Publications by authors named "Jinjun Ye"

28 Publications

  • Page 1 of 1

circRNA_0006470 promotes the proliferation and migration of gastric cancer cells by functioning as a sponge of miR-27b-3p.

Neoplasma 2021 Oct 11. Epub 2021 Oct 11.

Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, Dongguan, Guangdong, China.

Cancer pathogenesis is influenced by epigenetic alterations mediated by circular RNAs (circRNAs). In this study, we aimed to investigate the regulatory mechanisms and cytological function of hsa_circ_0006470/miR-27b-3p in gastric cancer (GC). CircRNA and microRNA expression in cancer cells were measured by the qRT-PCR method. A dual-luciferase reporter assay was performed to validate the binding of hsa_circ_0006470 with miR-27b-3p. hsa_circ_0006470 was silenced in AGS cells, and proliferation, migration, and invasion were tested via the CCK-8 assay and Transwell system, respectively. The autophagy in GC cells was assessed by marker protein detection and transmission electron microscope. The results showed that hsa_circ_0006470 expression was significantly elevated in GC cells, which was mainly distributed in cytoplasmic components and could directly bind with miR-27b-3p in GC cells. Silencing of hsa_circ_0006470 repressed cell proliferation, migration, and invasion, which may be through regulating miR-27b-3p/Receptor tyrosine kinase-like orphan receptor 1 (ROR1). Silencing of hsa_circ_0006470 also elevated LC3II and Beclin-1 and suppressed p62 protein abundances, which subsequently induced autophagy in AGS cells. Furthermore, we found that hsa_circ_0006470 promotes phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) expressing by sponging miR-27b-3p. In conclusion, hsa_circ_0006470 promoted GC cell proliferation and migration through targeting miR-27b-3p and suppressing autophagy machinery.
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http://dx.doi.org/10.4149/neo_2021_210222N235DOI Listing
October 2021

miR‑4306 inhibits the malignant behaviors of colorectal cancer by regulating lncRNA FoxD2‑AS1.

Mol Med Rep 2021 Oct 13;24(4). Epub 2021 Aug 13.

Department of General Surgery, Shenzhen Longgang Central Hospital, Shenzhen, Guangdong 518116, P.R. China.

MicroRNA (miR)‑4306 and FoxD2‑adjacent opposite strand RNA 1 (FOXD2‑AS1) are cancer‑related genes involved in tumor progression. However, the potential functional roles of miR‑4306 and FoxD2‑AS1 in colorectal cancer (CRC) development remain unknown. The present study aimed to investigate the biological functions and the molecular mechanisms of miR‑4306 and FoxD2‑AS1 in CRC. Reverse transcription‑quantitative PCR analysis was performed to determine the expression levels of FoxD2‑AS1 and miR‑4306 in CRC tissues and cell lines. Functional experiments, including Cell Counting Kit‑8, colony formation, cell cycle assays and western blotting, were conducted to examine the effects of FoxD2‑AS1 and miR‑4306 on the malignant behaviors of CRC cells. In addition, the relationship between FoxD2‑AS1 and miR‑4306 was assessed using a dual‑luciferase reporter assay and Pearson's correlation analysis. Compared with normal samples and cells, FoxD2‑AS1 expression was increased and miR‑4306 expression was decreased in CRC tissues and cells. Functional experiments demonstrated that silencing FoxD2‑AS1 inhibited proliferation and induced cell arrest at G/G phase in CRC cells, while the overexpression of FoxD2‑AS1 showed opposite results. Ki‑67 and proliferating cell nuclear antigen expression levels were decreased after transfection with small interfering RNA FoxD2‑AS1, but were increased after transfection with FoxD2‑AS1 overexpression plasmid. Furthermore, investigations into the underling mechanism revealed that FoxD2‑AS1 functioned as a molecular sponge of miR‑4306. The inhibitory effects of FoxD2‑AS1 silencing on CRC progression were reversed by miR‑4306 knockdown. Collectively, the present study demonstrated that FoxD2‑AS1 functioned as an oncogene in CRC progression, and that miR‑4306 could inhibit the malignant behaviors of CRC by regulating FoxD2‑AS1. Thus, the current study provided a promising therapeutic target for CRC treatment.
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http://dx.doi.org/10.3892/mmr.2021.12362DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383050PMC
October 2021

Long non-coding RNA TMPO-AS1 facilitates the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.

J Gastroenterol Hepatol 2021 Aug 9. Epub 2021 Aug 9.

Department of General Surgery, Longgang Central Hospital, Shenzhen, Guangdong, China.

Background: Colorectal cancer, as a common malignant carcinoma in the gastrointestinal tract, has a high mortality globally. However, the specific molecular mechanisms of long non-coding RNA (lncRNA) thymopoietin antisense transcript 1 (TMPO-AS1) in colorectal cancer were unclear.

Methods: We tested the expression level of TMPO-AS1 via qRT-PCR in colorectal cancer cells while the protein levels of branched chain amino acid transaminase 1 (BCAT1) and the stemness-related proteins were evaluated by Western blot analysis. Colony formation, EdU staining, TUNEL, flow cytometry and sphere formation assays were to assess the biological behaviors of colorectal cancer cells. Then, luciferase reporter, RIP and RNA pull down assay were applied for confirming the combination between microRNA-98-5p (miR-98-5p) and TMPO-AS1/BCAT1.

Results: TMPO-AS1 was aberrantly expressed at high levels in colorectal cancer cells. Silenced TMPO-AS1 restrained cell proliferation and stemness and promoted apoptosis oppositely while overexpressing TMPO-AS1 exerted the adverse effects. Furthermore, miR-98-5p was proven to a target of TMPO-AS1 inhibit cell progression in colorectal cancer. Additionally, BCAT1 was proved to enhance cell progression as the target of miR-98-5p, and it offset the effect of silenced TMPO-AS1 on colorectal cancer cells.

Conclusion: TMPO-AS1 promotes the progression of colorectal cancer cells via sponging miR-98-5p to upregulate BCAT1 expression.
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http://dx.doi.org/10.1111/jgh.15657DOI Listing
August 2021

A Multicenter Retrospective Study on the Prognosis of Stage III Unresectable Mutant Non-Small Cell Lung Cancer With Tyrosine Kinase Inhibitors Therapy.

Front Oncol 2021 12;11:692703. Epub 2021 Jul 12.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, School of Medicine, Southeast University, Nanjing, China.

Background: For unresectable stage III non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy is nowadays the standard treatment. Patients with advanced NSCLC harboring driver-gene mutations benefit from Tyrosine Kinase Inhibitors (TKIs) Therapy. In a real-world setting, there is room for exploring the benefit of TKIs in stage III unresectable NSCLC patients with mutation.

Methods: A total of 81 patients from the Jinling Hospital and the Jiangsu Cancer Hospital with stage III unresectable mutant NSCLC applied targeted therapy were enrolled in this retrospective study. Patients with first-line application of TKIs were followed up to gain the situation of surgery qualifications, progression-free survival and overall survival, so as to evaluate the survival prognosis, then whether patients benefit and what kind of patients benefit most from TKI monotherapy treatment or its combination are explored.

Results: The median progression-free survival of involved 81 patients was 13.87 months (95% confidence interval (CI): 11.66-16.08), and the median survival was 41.47 months (95%CI: 20.11-62.83). The 5-year survival rates were 91.0, 80.3, 56.1, 45.5, and 32.5%, respectively. After first-line TKI therapy, seven patients (8.6%) were reevaluated as eligible for surgery and proceeded to surgery. Although no characteristics were found to be statistical prognostic, younger female non-smokers still tended to have a better prognosis with longer progression free survival and overall survival.

Conclusions: TKIs are a viable option for mutant stage III unresectable NSCLC patients who have achieved good clinical benefit from TKI. Patients who cannot tolerate chemoradiotherapy, especially those with driver gene mutations, can choose targeted therapy for first-line treatment.
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http://dx.doi.org/10.3389/fonc.2021.692703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311792PMC
July 2021

Combined targeting of vascular endothelial growth factor C (VEGFC) and P65 using miR-27b-3p agomir and lipoteichoic acid in the treatment of gastric cancer.

J Gastrointest Oncol 2021 Feb;12(1):121-132

Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Dongguan Third Clinical Hospital of Guangdong Medical University, Dongguan, China.

Background: Gastric cancer is the second leading cancer-related mortality worldwide and more effective treatment strategies are urgently needed to combat the disease. Using lipoteichoic acid (LTA) and miR-27b-3p agomir, we aimed to assess the efficacy of this combination of therapies in treating gastric cancer.

Methods: The RNA levels of miR-27b-3p, FOXO3, MET, KRAS, vascular endothelial growth factor C (VEGFC), TSC1, and P65 were analyzed by quantified-PCR (Q-PCR) and the cell viability of AGS cells was analyzed by MTT. Confirm Luciferase reporter assays were used to explore the putative miR-27b-3p binding sites and Western blot analyzed the protein level of GAPDH, VEGFC, P65, AKT, and phosphorylated-AKT (p-AKT). The level of P65 in both the cytoplasm and nucleus of AGS cells was visualized by immunofluorescence assay. Subcutaneous xenograft models of gastric cancer were established, and mice were treated with miR-27b-3p agomir, LTA, or both. Hematoxylin-eosin staining and Ki-67 immunohistochemistry analysis of tumor tissues were then performed.

Results: The results showed that the decreased expression of miR-27b-3p in gastric cancer cell lines inhibited the viability of AGS cells, and VEGFC was confirmed as the target of miR-27b-3p. In addition, ectopic expression of miR-27b-3p significantly inhibited the AKT pathway in AGS and N87 cells, and LTA suppressed the proliferation of gastric cancer cells by inhibiting the NF-κB pathway. In an established xenograft model, both miR-27b-3p agomir alone and LTA treatment alone inhibited tumor growth and treatment which combined the two showed an even stronger inhibitory effect.

Conclusions: Taken together, the combined use of LTA and miR-27b-3p agomir exhibited a synergistic effect in the treatment of gastric cancer.
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http://dx.doi.org/10.21037/jgo-21-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944161PMC
February 2021

Involved-Field Irradiation in Definitive Chemoradiotherapy for Locoregional Esophageal Squamous Cell Carcinoma: Results From the ESO-Shanghai 1 Trial.

Int J Radiat Oncol Biol Phys 2021 08 5;110(5):1396-1406. Epub 2021 Mar 5.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address:

Purpose: To evaluate the feasibility and efficacy of involved-field irradiation in definitive chemoradiation therapy for locoregional esophageal squamous cell carcinoma.

Methods And Materials: Patterns in recurrence and elective nodal failure were analyzed in patients from the previously published ESO-Shanghai 1 trial, who received definitive chemoradiation therapy with involved-field irradiation to 61.2 Gy in 34 fractions using intensity modulated radiation therapy planning. Nodal regions were delineated using the lymph node map from the sixth edition of the American Joint Committee on Cancer staging system. Elective nodal failure was defined as recurrence in the regional nodal area outside the planning target volume. Extensive elective nodal failure, defined as an extensive nodal area regardless of tumor location, was calculated for additional analysis. The incidental (ie, mean) irradiation dose of each node and each region was evaluated.

Results: With a median follow-up of 48.7 months among survivors, the 3-year actuarial rate for overall survival was 53.6%, and the median overall survival was 44.8 months (95% confidence interval, 34.6-55.0). Of the 436 patients included in this study, 258 patients (59.2%) experienced treatment failure. Elective nodal failure was experienced by 37 patients (8.5%), 7 (1.6%) of whom encountered nodal-only failure. The 3-year actuarial rates of elective nodal control and elective nodal-only control were 89.7% and 97.9%, respectively. The median incidental dose of these nodes was 33.2 Gy (interquartile range [IQR], 1.3-50.7 Gy). The median distance of each node to the planning target volume was 1.4 cm (IQR, 0.6-4.9 cm). Extensive elective nodal failure was experienced by 51 patients (11.6%), and 20 (4.6%) patients had nodal-only failure. The 3-year extensive elective nodal control and extensive elective nodal control-only rates were 86.0% and 94.3%, respectively. The median incidental dose of these nodes was 23.2 Gy (IQR, 1.1-53.5 Gy). The median distance of each node to the planning target volume was 2.0 cm (IQR, 0.6-5.5 cm).

Conclusion: Involved-field irradiation can achieve a low rate of isolated nodal failure and a satisfactory survival outcome. The use of elective nodal irradiation may be unnecessary in definitive chemoradiation therapy for the treatment of locoregional esophageal squamous cell carcinoma.
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http://dx.doi.org/10.1016/j.ijrobp.2021.02.053DOI Listing
August 2021

Dkk1 inhibits malignant transformation induced by Bmi1 via the β-catenin signaling axis in WB-F344 oval cells.

FEBS Open Bio 2021 Jul 9;11(7):1854-1866. Epub 2021 Jun 9.

Department of General Surgery, Longgang Central Hospital, Shenzhen, China.

Dickkopf-1 (Dkk1) is an inhibitor of Wnt signaling involved in cancer cell proliferation, apoptosis, and migration and angiogenesis. It was previously reported that B cell-specific Moloney mouse leukemia virus integration site 1 (Bmi1) activates the Wnt pathway by inhibiting the expression of DKK1 in breast cancer cell lines and 293T cells. Bmi1 and DKK1 are highly expressed in liver samples taken by biopsy from patients with hepatitis B virus-related hepatocellular carcinoma (HCC), but the effect of both Bmi1 and DKK1 on the carcinogenesis of adult hepatic stem cells (oval cells) has not previously been reported. In this study, we used WB-F344 cells to explore the function and regulation of Dkk1 upon Bmi1 treatment. Overexpression of Dkk1 repressed differentiation, proliferation, and migration induced by Bmi1 but promoted the apoptosis of hepatic WB-F344 oval cells. In addition, Dkk1 reduced the enhancement of β-catenin levels induced by Bmi1. Finally, we used transcriptome sequencing to perform a comprehensive evaluation of the transcriptome-related changes in WB-F344 oval cells induced by Dkk1 and Bmi1. These results may provide evidence for future studies of the pathogenesis of HCC and the design of possible therapies.
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http://dx.doi.org/10.1002/2211-5463.13132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255841PMC
July 2021

Local therapy for oligometastatic esophageal squamous cell carcinoma: a prospective, randomized, Phase II clinical trial.

Future Oncol 2021 Apr 25;17(11):1285-1293. Epub 2021 Feb 25.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai, 200032, China.

For patients with oligometastatic esophageal squamous cell carcinoma, the efficacy of local therapy is still controversial because of patient selection and lack of adequate controls in most studies. Here the authors design the ESO-Shanghai 13 trial, a prospective, multicenter, randomized, Phase II trial, to assess the impact of combined local therapy and systemic therapy on progression and survival compared with systemic therapy alone for patients with four or less metastases. A total of 102 patients will be recruited over 3 years from approximately five centers and randomized in a 1:1 ratio to receive either systemic therapy alone or systemic therapy and local therapy, such as radiation, surgery and thermal ablation. The primary endpoint is progression-free survival. The secondary endpoints are overall survival, local control, toxicity and quality of life. Clinical trial registration: NCT03904927 (ClinicalTrials.gov).
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http://dx.doi.org/10.2217/fon-2020-0873DOI Listing
April 2021

Development of a prognostic signature for esophageal cancer based on nine immune related genes.

BMC Cancer 2021 Feb 4;21(1):113. Epub 2021 Feb 4.

Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & Nanjing Medical University Affiliated Cancer Hospital, 42 Bai Zi Ting Road, Nanjing, 210000, Jiangsu, China.

Background: Function of the immune system is correlated with the prognosis of the tumor. The effect of immune microenvironment on esophageal cancer (EC) development has not been fully investigated.

Methods: This study aimed to explore a prognostic model based on immune-related genes (IRGs) for EC. We obtained the RNA-seq dataset and clinical information of EC from the Cancer Genome Atlas (TCGA).

Results: We identified 247 upregulated IRGs and 56 downregulated IRGs. Pathway analysis revealed that the most differentially expressed IRGs were enriched in Cytokine-cytokine receptor interaction. We further screened 13 survival-related IRGs and constructed regulatory networks involving related transcription factors (TFs). Finally, a prognostic model was constructed with 9 IRGs (HSPA6, S100A12, CACYBP, NOS2, DKK1, OSM, STC2, NGPTL3 and NR2F2) by multivariate Cox regression analysis. The patients were classified into two subgroups with different outcomes. When adjusted with clinical factors, this model was verified as an independent predictor, which performed accurately in prognostic prediction. Next, M0 and M2 macrophages and activated mast cells were significantly enriched in high-risk group, while CD8 T cells and regulatory T cells (Tregs) were significantly enriched in low-risk group.

Conclusions: Prognosis related IRGs were identified and a prognostic signature for esophageal cancer based on nine IRGs was developed.
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http://dx.doi.org/10.1186/s12885-021-07813-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860013PMC
February 2021

LINC00963 affects the development of colorectal cancer via MiR-532-3p/HMGA2 axis.

Cancer Cell Int 2021 Feb 3;21(1):87. Epub 2021 Feb 3.

Department of General Surgery, Shenzhen Longgang Central Hospital, No.6082 Longgang Avenue, Longgang District, Shenzhen, 518116, Guangdong, China.

Background: LINC00963 is high-expressed in various carcinomas, but its expression and function in colorectal cancer (CRC) have not been explored. This study explored the role and mechanism of LINC00963 in CRC.

Methods: The expression of LINC00963 in CRC and its relationship with prognosis were examined by starBase and survival analysis. The effects of LINC00963, miR-532-3p and HMGA2 on the biological characteristics and EMT-related genes of CRC cells were studied by RT-qPCR, CCK-8, clone formation experiments, flow cytometry, scratch test, Transwell, and Western blot. Xenograft assay and immunohistochemistry were performed to verify the effect of LINC00963 on tumor growth. The correlation among LINC00963, miR-532-3p, and HMGA2 was analyzed by bioinformatics analysis, luciferase assay, and Pearson test.

Results: LINC00963 was high-expressed in CRC, and this was associated with poor prognosis of CRC. Silencing LINC00963 inhibited the activity, proliferation, migration, and invasion of CRC cells, MMP-3 and MMP-9 expressions, moreover, it also blocked cell cycle progression, and inhibited tumor growth and Ki67 expression. However, overexpression of LINC00963 showed the opposite effects to silencing LINC00963. LINC00963 targeted miR-532-3p to regulate HMGA2 expression. Down-regulation of miR-532-3p promoted cell proliferation, migration and invasion, and expressions of MMP-3 and MMP-9, and knockdown of HMGA2 reversed the effect of miR-532-3p inhibitor. Up-regulation of miR-532-3p inhibited the biological functions of CRC cells, and overexpression of HMGA2 reversed the miR-532-3p mimic effect.

Conclusion: LINC00963 affects the development of CRC through the miR-532-3p/HMGA2 axis.
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http://dx.doi.org/10.1186/s12935-020-01706-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860506PMC
February 2021

LncRNA FAM230B Promotes Gastric Cancer Growth and Metastasis by Regulating the miR-27a-5p/TOP2A Axis.

Dig Dis Sci 2021 08 10;66(8):2637-2650. Epub 2020 Sep 10.

Department of Clinical Laboratory, SSL Central Hospital of Dongguan City, Affiliated Dongguan Shilong People's Hospital of Southern Medical University, 1 Xianglong Road, Dongguan City, 510080, Guangdong Province, China.

Aim: Long non-coding RNAs serve as key components of competing endogenous RNA (ceRNA) networks that underlie tumorigenesis. We investigated the pathogenic roles of lncRNA FAM230B and its molecular mechanism in gastric cancer (GC).

Method: The levels of FAM230B expression in five gastric cancer cell lines and in human gastric mucosal cells were compared by quantitative RT-PCR. To analyze the function of FAM230B in GC, we overexpressed FAM230B in AGS cells, silenced FAM230B in MGC-803 cells, and tested the effect of FAM230B on tumor growth in nude mice. The interaction between miR-27a-5p and FAM230B was predicted by a bioinformatics analysis and then verified with a dual-luciferase reporter assay. We also further investigated the role and mechanism of FAM230B by forcing overexpression of miR-27a-5p in MGC-803 gastric cancer cells.

Results: We found that FAM230B was highly expressed in gastric cancer cell lines and mainly located in the cytoplasm. FAM230B overexpression promoted the proliferation, migration, and invasion of AGS cells and repressed their apoptosis; it also facilitated tumor growth in vivo. In contrast, FAM230B knockdown suppressed the proliferation, migration, and invasion of MGC0803 cells, but enhanced their apoptosis and inhibited tumor growth in vivo. MiR-27a-5p expression was suppressed by FAM230B overexpression in AGS cells. MiR-27a-5p inhibited the proliferation, migration, and invasion of gastric cancer cells, and promoted the apoptosis of gastric cancer cells by reducing TOP2A (topoisomerase 2 alpha) expression.

Conclusion: Our study showed that lncRNA FAM230B might function to promote GC. FAM230B functioned as a ceRNA by sponging miR-27a-5p and enhancing TOP2A expression.
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http://dx.doi.org/10.1007/s10620-020-06581-zDOI Listing
August 2021

Curcumol Inhibits Lung Adenocarcinoma Growth and Metastasis via Inactivation of PI3K/AKT and Wnt/-Catenin Pathway.

Oncol Res 2021 Sep 16;28(7):685-700. Epub 2020 Jun 16.

Department of Thoracic Surgery, Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and Nanjing Medical University Affiliated Cancer HospitalNanjingP.R. China.

Curcumol (Cur), isolated from the Traditional Chinese Medical plant , is the bioactive component of sesquiterpene reported to possess antitumor activity. However, its bioactivity and mechanisms against lung adenocarcinoma are still unclear. We investigated its effect on lung adenocarcinoma and elucidated its underlying molecular mechanisms. In vitro, Cur effectively suppressed proliferation, migration, and invasion of lung adenocarcinoma cells A549 and H460, which were associated with the altered expressions of signaling molecules, including p-AKT, p-PI3K, p-LRP5/6, AXIN, APC, GSK3 and p--catenin, matrix metalloproteinase (MMP)-2, and MMP-9. Furthermore, Cur significantly induced cell apoptosis of A549 and H460 by promoting the expression of Bax, caspase 3, and caspase 9 and suppressing the expression of Bcl-2, and arrested the cell cycle at the G/G phase by lowering the levels of cyclin D1, CDK1, and CDK4. In vivo experiment revealed that Cur could inhibit lung tumor growth and lung metastasis, which were consistent with these in vitro results. In xenograft model mice, Cur strongly decreased tumor weight and tumor volume, which may be related to the downregulation of p-AKT and p-PI3K by immunofluorescence analysis. In addition, a lung metastasis model experiment suggested that Cur dramatically decreased the ratio of lung/total weight, tumor metastatic nodules, and the expressions of MMP-2 and MMP-9 in lung tissues compared with the control. Overall, these data suggested that the inhibitory activity of Cur on lung adenocarcinoma via the inactivation of PI3K/Akt and Wnt/-catenin pathways, at least in part, indicates that curcumol may be a potential antitumor agent for lung adenocarcinoma therapy.
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http://dx.doi.org/10.3727/096504020X15917007265498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420902PMC
September 2021

Mitofusin-2 (Mfn-2) Might Have Anti-Cancer Effect through Interaction with Transcriptional Factor SP1 and Consequent Regulation on Phosphatidylinositol Transfer Protein 3 (PITPNM3) Expression.

Med Sci Monit 2020 Jan 19;26:e918599. Epub 2020 Jan 19.

Department of General Surgery, Longgang Central Hospital of Shenzhen, Shenzhen, Guangdong, China (mainland).

BACKGROUND The aim of this study was to explore the influence of mitofusin-2 (Mfn-2) on phosphatidylinositol transfer protein 3 (PITPNM3) and tumor growth and the potential mechanism behind the regulation of Mfn-2 on PITPNM3 in hepatic carcinoma cell line SMMC-7721. MATERIAL AND METHODS We obtained promoter sequence of PITPNM3 gene from University of Santa Cruz (UCSC) genomic database, and we predict transcriptional factor of PITPNM3 genes by JASPAR database. Target transcription factor was determined by comparison of binding sites number for promoter. SMMC-7721 cells were transfected with expression plasmid containing Mfn-2, transcription factor gene and PITPNM3. The cells transfected with empty vector were used as control. Real-time polymerase chain reaction was used to determine the mRNA level of target genes. Co-immunoprecipitation (Co-IP) assay was used to determine the interaction between Mfn-2 and target transcription factor. Chromatin immunoprecipitation assay (ChIP) assay was used to determine the binding of transcription factor with PITPNM3 promoter. Tumorigenicity assay was used to compare the effect of Mfn-2, SP1, and PITPNM3 on tumor development. RESULTS SP1 was selected as the target transcriptional factor. In the Co-IP assay, Mfn-2 was shown to interact with SP1. In the ChIP assay Mfn-2 transfection resulted in decreased binding number of SP1 with PITPNM3 promoter. Furthermore, PITPNM3 mRNA levels were significantly increased in SMMC-7721 cells transfected with SP1 but were decreased after transfection with Mfn-2. In nude mice, PITPNM3 and SP1 upregulation lead to larger tumor lump and conversely Mfn-2 upregulation lead to smaller tumor lump. CONCLUSIONS Mfn-2 could suppress expression of PITPNM3 through interaction with transcription factor SP1; Mfn-2 may have anti-tumor activity; SP1 and PITPNM3 may promote tumor development.
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http://dx.doi.org/10.12659/MSM.918599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988473PMC
January 2020

CDKN3 promotes cell proliferation, invasion and migration by activating the AKT signaling pathway in esophageal squamous cell carcinoma.

Oncol Lett 2020 Jan 11;19(1):542-548. Epub 2019 Nov 11.

Department of Radiotherapy, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu 210000, P.R. China.

In China, esophageal squamous cell carcinoma (ESCC), capable of direct invasion and early metastasis, exhibits high mortality. Identification of the molecular basis driving ESCC progression and development of new diagnostic biomarkers are urgently needed. Cyclin-dependent kinase inhibitor 3 (CDKN3) performs crucial roles in the modulation of tumor development. The present study aimed to explore the functions and underlying mechanism of CDKN3 in regulating ESCC cell proliferation and invasion. The expression levels of CDKN3 in ESCC cells were evaluated by reverse transcription-quantitative PCR. Cell counting kit-8 and colony forming assays were used to evaluate cell viability. Wound-healing assay was performed to explore cell migration. Transwell invasion analysis was conducted to investigate the invasive capacity of ESCC cells. Protein levels were detected by western blot assay. The results demonstrated that the expression of CDKN3 was significantly upregulated in ESCC tissues, as predicted using the UALCAN and Gene Expression Omnibus databases. PCR and western blot assays confirmed that CDKN3 was upregulated in ESCC cell lines. Functional assays revealed that CDKN3 knockdown with small interfering RNA decreased the ability of ESCC cells to proliferate, invade and migrate and suppressed G1/S transition. Further mechanistic analyses demonstrated that CDKN3 promoted cell proliferation and invasion by activating the AKT signaling pathway in ESCC cells. To the best of our knowledge, the present study is the first to identify the functions of CDKN3 in ESCC and provide evidence that CDKN3 regulates tumor progression by activating the AKT signaling pathway. Therefore, CDKN3 may serve as a potential effective therapeutic target for ESCC treatment.
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http://dx.doi.org/10.3892/ol.2019.11077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924098PMC
January 2020

Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial.

J Clin Oncol 2019 07 28;37(20):1695-1703. Epub 2019 Mar 28.

1 Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: This trial aimed to assess the efficacy and safety of the paclitaxel plus fluorouracil regimen versus the cisplatin plus fluorouracil regimen in definitive concurrent chemoradiotherapy (dCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).

Patients And Methods: Patients with locally advanced ESCC were enrolled and randomly assigned to either the paclitaxel plus fluorouracil group or the cisplatin plus fluorouracil group. The patients in the paclitaxel plus fluorouracil group were treated with paclitaxel and fluorouracil one cycle per week in dCRT for five cycles followed by paclitaxel and fluorouracil one cycle per month in consolidation chemotherapy for two cycles. The patients in the cisplatin/5-fluorouracil group were treated with cisplatin and fluorouracil one cycle per month in dCRT for two cycles followed by two cycles in consolidation chemotherapy. The radiotherapy dose was 61.2 Gy delivered in 34 fractions. The primary end point was 3-year overall survival (OS).

Results: Four hundred thirty-six patients with ESCC in six centers were recruited at a 1:1 ratio between April 2012 and July 2015. The median follow-up of the surviving patients was 48.7 months (interquartile range, 42.6-60.9). The 3-year OS was 55.4% in the paclitaxel plus fluorouracil group and 51.8% in the cisplatin plus fluorouracil group (hazard ratio, 0.905 [95% CI, 0.698 to 1.172]; = .448). The 3-year progression-free survival was also not significantly different between the paclitaxel plus fluorouracil group and the cisplatin plus fluorouracil group (43.7% 45.5%, respectively; hazard ratio, 0.973 [95% CI, 0.762 to 1.243]; = .828). Compared with the cisplatin plus fluorouracil group, the paclitaxel plus fluorouracil group had significantly lower incidences of acute grade 3 or higher anemia, thrombocytopenia, anorexia, nausea, vomiting, and fatigue ( < .05), but higher incidences of acute grade 3 or higher leukopenia, radiation dermatitis, and radiation pneumonitis ( < .05).

Conclusion: The paclitaxel plus fluorouracil regimen did not significantly prolong the OS compared with the standard cisplatin plus fluorouracil regimen in dCRT in patients with locally advanced ESCC.
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http://dx.doi.org/10.1200/JCO.18.02122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6638596PMC
July 2019

miR-130a-3p regulated TGF-β1-induced epithelial-mesenchymal transition depends on SMAD4 in EC-1 cells.

Cancer Med 2019 03 11;8(3):1197-1208. Epub 2019 Feb 11.

Jiangsu Cancer Hospital, Jiangsu Institue of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu, China.

Metastasis and invasion are the primary causes of malignant progression in esophageal squamous cell carcinoma (ESCC). Epithelial-mesenchymal transition (EMT) is crucial step of acquisition of "stemness" properties in tumor cells. However, the mechanism of esophageal cancer metastasis remains unclear. This research was designed to explore the role and mechanism of SMAD4 and miR-130a-3p in the progression of transforming growth factor-β (TGF-β)-induced EMT in vivo and in vitro. The expression of miR-130a-3p in ESCC cell line and normal esophageal epithelial cell was determined by RT-qPCR. The protein expression levels of TGF-β-induced changes in EMT were analyzed by western blotting and immunofluorescence. Dual-luciferase report assays were used to validate the regulation of miR-130a-3p-SMAD4 axis. The effect of miR-130a-3p and SMAD4 in TGF-β-induced migration, invasion in the ESCC cell line EC-1 was investigated by wound healing assays and Transwell assays. Here we found that knocked down SMAD4 could partially reverse TGF-β-induced migration, invasion, and EMT progression in the ESCC cell line EC-1. miR-130a-3p, which directly targets SMAD4, is down-regulated in ESCC. miR-130a-3p inhibits the migration and invasion of EC-1 cells both in vitro and in vivo. Finally, miR-130a-3p inhibits TGF-β-induced EC-1 cell migration, invasion, and EMT progression in a SMAD4-dependent way. In conclusion, this study provides new insights into the mechanism underlying ESCC metastasis. The TGF-β/miR-130a-3p/SMAD4 pathway could be potential targets for clinical treatment of ESCC.
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http://dx.doi.org/10.1002/cam4.1981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434193PMC
March 2019

Comparison of paclitaxel in combination with cisplatin (TP), carboplatin (TC) or fluorouracil (TF) concurrent with radiotherapy for patients with local advanced oesophageal squamous cell carcinoma: a three-arm phase III randomized trial (ESO-Shanghai 2).

BMJ Open 2018 10 21;8(10):e020785. Epub 2018 Oct 21.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Introduction: Concurrent chemoradiation is the standard therapy for patients with local advanced oesophageal carcinoma unsuitable for surgery. Paclitaxel is an active agent against oesophageal cancer and it has been proved as a potent radiation sensitiser. There have been multiple studies evaluating paclitaxel-based chemoradiation in oesophageal cancer, of which the results are inspiring. However, which regimen, among cisplatin (TP), carboplatin (TC) or fluorouracil (TF) in combination with paclitaxel concurrent with radiotherapy, provides best prognosis with minimum adverse events is still unknown and very few studies focus on this field. The purpose of this study is to confirm the priority of TF to TP or TF to TC concurrent with radiotherapy in terms of overall survival and propose a feasible and effective plan for patients with local advanced oesophageal cancer.

Methods And Analysis: ESO-Shanghai 2 is a three-arm, multicenter, open-labelled, randomised phase III clinical trial. The study was initiated in July 2015 and the duration of inclusion is expected to be 4 years. The study compares two pairs of regimen: TF versus TP and TF versus TC concurrent with definitive radiotherapy for patients with oesophageal squamous cell carcinoma (OSCC). Patients with histologically confirmed OSCC (clinical stage II, III or IVa based on the sixth Union for International Cancer Control-tumour, node, metastasis classification) and without any prior treatment of chemotherapy, radiotherapy or surgery against oesophageal cancer will be eligible. A total of 321 patients will be randomised and allocated in a 1:1:1 ratio to the three treatment groups. Patients are stratified by lymph node status (N0, N1, M1a). The primary endpoint is overall survival and the secondary endpoint is progression-free survival and adverse events.

Ethics And Dissemination: This trial has been approved by the Fudan University Shanghai Cancer Centre Institutional Review Board. Trial results will be disseminated via peer reviewed scientific journals and conference presentations.

Trial Status: The trial was initiated in July 2015 and is currently recruiting patients in all of the participating institutions above.

Trial Registration Number: NCT02459457.
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http://dx.doi.org/10.1136/bmjopen-2017-020785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196866PMC
October 2018

Integrin αvβ6 Promotes Lung Cancer Proliferation and Metastasis through Upregulation of IL-8-Mediated MAPK/ERK Signaling.

Transl Oncol 2018 Jun 21;11(3):619-627. Epub 2018 Mar 21.

Department of radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 210000, PRC. Electronic address:

Lung cancer is notorious for high morbidity and mortality around the world. Interleukin (IL)-8, a proinflammatory chemokine with tumorigenic and proangiogenic effects, promotes lung cancer cells growth and migration and contributes to cell aggressive phenotypes. Integrin αvβ6 is a receptor of transmembrane heterodimeric cell surface adhesion, and its overexpression correlates with poor survival from non-small cell lung cancer. However, the cross talk between αvβ6 and IL-8 in lung cancer has not been characterized so far. Herein, human lung cancer samples were analyzed, and it revealed that the immunohistochemical and mRNA expression of integrin αvβ6 was significantly correlated with the expression of IL-8. Furthermore, in vitro, integrin αvβ6 increased cell proliferation, migration, and invasion by impairing the expressions of MMP-2 and MMP-9 and inhibited cell apoptosis in human lung cancer cells A549 and H460. In addition, integrin αvβ6 upregulated IL-8 expression through activating MAPK/ERK signaling. The in vivo experiment showed that integrin αvβ6 promoted tumor growth in xenograft model mice by accelerating tumor volume and reducing apoptosis. Meanwhile, lung metastasis model experiment suggested that integrin αvβ6 stimulated tumor metastasis with the increase of lung/total weight and tumor nodules. Simultaneously, integrin αvβ6 upregulated IL-8 expression detected by both Western blots and immunohistochemistry, along with the activation of MAPK/ERK signaling. Overall, these data suggested that, in vitro and in vivo, integrin αvβ6 promoted lung cancer proliferation and metastasis, at least in part, through upregulation of IL-8-mediated MAPK/ERK signaling. Thus, the inhibition of integrin αvβ6 and IL-8 may be the key for the treatment of lung cancer.
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http://dx.doi.org/10.1016/j.tranon.2018.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002349PMC
June 2018

Sepia Ink Oligopeptide Induces Apoptosis of Lung Cancer Cells via Mitochondrial Pathway.

Cell Physiol Biochem 2018 7;45(5):2095-2106. Epub 2018 Mar 7.

Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Jiangsu Cancer Hospital, Nanjing, China.

Background/aims: Our previous study suggested the anti-tumor activity of sepia ink oligopeptide (SIO). Here we sought to investigate the underlying molecular mechanism.

Methods: Cell proliferation was evaluated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was determined by Annexin V/Propidium Iodide (PI) staining. The mitochondria pathway was characterized by quantification of Bcl-2, Bax, Caspase-9 and Cyto-C. The death receptor pathway was analyzed by determinement of Fas, Caspase-8 and NIK. The endoplasmic reticulum (ER)-dependent pathway was determined by measurement the expression of CHOP, Caspase-12, GRP78 and Calpain. The associated gene expression was quantified by RT-PCR and protein level was determined by immunoblotting.

Results: We demonstrated treatment with structurally modified SIO (CSIO, 5 µM) significantly inhibited cell proliferation and induced apoptosis in lung cancer cell line A549. The mitochondrial pathway, death receptor pathway and ER stress induced apoptosis were stimulated upon CSIO treatment. The administration with respective inhibitors including midiv-1 (50 µM for 2 h), PDTC (20 µM PDTC for 30 min) and ALLN (20 mM ALLN for 5 h) readily reversed the apoptosis inducing effect of CSIO.

Conclusion: Our data demonstrates that CSIO is capable of induction apoptosis in lung cancer cell line, which is mediated by all three classical apoptotic pathways. Our results warrant further in vivo investigations of the anti-tumor potential of CSIO.
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http://dx.doi.org/10.1159/000488046DOI Listing
May 2018

A randomized phase 3 trial comparing paclitaxel plus 5-fluorouracil versus cisplatin plus 5-fluorouracil in Chemoradiotherapy for locally advanced esophageal carcinoma-the ESO-shanghai 1 trial protocol.

Radiat Oncol 2018 Feb 27;13(1):33. Epub 2018 Feb 27.

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 270 DongAn Road, Shanghai, 200032, China.

Background: Concurrent chemoradiotherapy is a standard modality for locally advanced esophageal squamous cell carcinoma (ESCC) patients. Cisplatin combined with 5-fluorouracil continuous infusion (PF) remains the standard concurrent chemotherapy regimen. However, radiotherapy concurrent with PF showed a high incidence of severe side effects. Paclitaxel showed a promising radiosensitivity enhancement in the treatment of esophageal carcinoma in both vitro and vivo studies. The ESO-Shanghai 1 trial examines the hypothesis that paclitaxel plus 5-fluorouracil (TF) concurrent with radiotherapy has better overall survival and lower toxicity for patients with local advanced ESCC.

Method: Four hundred thirty-six ESCC patients presenting with stage IIa to IVa will be enrolled in a prospective multicenter randomized phase 3 study. Patients will be randomized to either concurrent chemoradiotherapy with PF (cisplatin 25 mg/m/d, d1-3, plus 5-fluorouracil 1800 mg/m, continuous infusion for 72 h) once every 4 weeks for 2 cycles followed by consolidation chemotherapy for 2 cycles or concurrent chemoradiotherapy with weekly TF (5-fluorouracil 300 mg/m, continuous infusion for 96 h plus paclitaxel 50 mg/m, d1) for 5 weeks followed by consolidation chemotherapy (5-fluorouracil 1800 mg/m, continuous infusion for 72 h, plus paclitaxel 175 mg/m d1) once every 4 weeks for 2 cycles. The radiotherapy dose is 61.2 Gy delivered in 34 fractions to the primary tumor including lymph nodes. The primary end-point is the 3-yr overall survival analyzed by intention to treat. The secondary endpoints are disease progression-free survival, local progression-free survival, and number and grade of participants with adverse events.

Discussion: The aim of this phase 3 study is to determine whether the TF regimen could replace the standard PF regimen for inoperable ESCC patients. An overall survival benefit of 12% at 3 years should be expected in the TF group to achieve this goal.

Trial Registration: ClinicalTrials.gov Identifier: NCT01591135 . Registered 18 April 2012.
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http://dx.doi.org/10.1186/s13014-018-0979-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828310PMC
February 2018

Patterns of distant organ metastases in esophageal cancer: a population-based study.

J Thorac Dis 2017 Sep;9(9):3023-3030

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Background: Esophageal cancer is the eighth most common cancer worldwide. The prognosis of esophageal cancer patients is dismal, especially those with distant organ metastasis. However, there are few studies describing the patterns of distant metastasis in esophageal cancer systematically.

Methods: We gathered the data from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2013. Categorical variables were analyzed by the Pearson Chi square test, and continuous variables were analyzed by the two-sample t test. Survival estimation and comparison among different variables were performed using Kaplan-Meier method. A multivariable logistic regression model was used to calculate odds ratios (OR) for sex, age, anatomical site, and histological type on specific metastases. Proportional hazards regression model was conducted to obtain adjusted hazard ratio (HRs) for different predictors of overall survival.

Results: A total of 9,934 patients were eligible. Liver was the most common metastatic site in the patients of esophageal cancer and followed by lung, bone and brain. Some clinical features, including age, sex, histology type and histologic grade were independent risk factors for different sites of metastasis. Younger age, poorer differentiation, adenoma type and more metastatic sites might lead to poorer prognosis.

Conclusions: Our findings revealed the patterns of metastasis in esophageal cancer, which could help clinicians to identify patients with metastasis and provide proper treatment.
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http://dx.doi.org/10.21037/jtd.2017.08.72DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708381PMC
September 2017

Identification of DBCCR1 as a suppressor in the development of lung cancer that is associated with increased DNA methyltransferase 1.

Oncotarget 2017 May;8(20):32821-32832

Department of Chemotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, Nanjing 210000, Jiangsu, China.

Accumulating evidence has pointed to a role of the CpG island hypermethylation in the regulation of cancer-related genes in tumor progression. However, the biological impacts in cancer pathogenesis associated with down-regulation of such gene targets remains elusive. Here we focused on a potential target of hypermethylation, DBCCR1 (deleted in bladder cancer chromosome region 1), a gene encoding a candidate tumor suppressor. We found that the expression of DBCCR1 is significantly lower in the lung cancer tissues compared with adjacent non-tumor tissues of patients. Importantly, the decreased DBCCR1 was found correlated with more advanced stages of cancer, and with a significantly shorter survival of patients. Genetic silencing DBCCR1 in human lung cancer cell line A549 resulted in an enhanced proliferation, migration, and invasion capacity. Conversely, restoring DBCCR1 expression blocked the growth and inhibited the ability of cancer cell in migration and invasion. Interestingly, DBCCR1 attenuates the expression of DNMT1 (DNA methyltransferase 1), suggesting a reciprocal regulation between genetic silencing of cancer suppressor genes and activating DNA methylation. Our data thus implicates DBCCR1 downregulation as a potential module in the pathogenesis of lung cancer through DNA methylation.
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http://dx.doi.org/10.18632/oncotarget.15826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464830PMC
May 2017

Sepia ink oligopeptide induces apoptosis and growth inhibition in human lung cancer cells.

Oncotarget 2017 Apr;8(14):23202-23212

Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing 210000, Jiangsu, China.

Sepia ink oligopeptide (SIO), as a tripeptide extracted from Sepia ink, could be used as an inducer of apoptosis in human prostate cancer cells. We designed a cyclo-mimetic peptide of SIO by introducing a disulfide bond to stabilize the native peptide into beta turn structure, and produced a peptide with higher cell permeability and stability. Through labeling an FITC to the N-terminus of the peptide, the cell permeability was examined. Stabilized peptide showed enhanced cellular uptake than linear tripeptide as indicated by flow cytometry and cell fluorescent imaging. The high intracellular delivery of stable SIO could more efficiently inhibit cell proliferation and induce apoptosis. Furthermore, the expression of the anti-apoptotic protein Bcl-2 was down-regulated, whereas pro-apoptotic proteins P53 and caspase-3 were up-regulated by stable SIO. In conclusion, our study is the first to use stable SIO to induce apoptosis in two lung cancer cells A549 and H1299.
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http://dx.doi.org/10.18632/oncotarget.15539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410297PMC
April 2017

miR-186 regulates chemo-sensitivity to paclitaxel via targeting MAPT in non-small cell lung cancer (NSCLC).

Mol Biosyst 2016 10;12(11):3417-3424

Department of Chemotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Road, Nanjing 210000, Jiangsu, China.

miR-186 has been reported to be implicated in tumorigenesis and chemoresistance in a few cancer types. However, its role in regulating chemoresistance has not been investigated in non-small cell lung cancer (NSCLC). To examine the effects of miR-186 on chemosensitivity in NSCLC, an miR-186 mimic and inhibitor were transfected, followed by CellTiter-Glo® assay in NSCLC cell lines. Western blot and luciferase assay were performed to investigate the direct targeting of miR-186. A xenograft mouse model was used to examine the in vivo chemosensitizing function of miR-186. We found that overexpression of miR-186 sensitized A549 and H1299 cells to paclitaxel, whereas inhibition of miR-186 conferred resistance in these cells. MAPT was the direct target of miR-186 which was required for the regulatory role of miR-186 in chemoresistance. This chemosensitizing function was partially due to the induction of the p53 mediated apoptotic pathway. The miR-186 mimic enhanced the tumor growth inhibitory effects of paclitaxel in A549 xenografts. In addition, miR-186 was found to be down-regulated in NSCLC patients who were chemoresistant and this down-regulation was associated with poor survival. Taken together, our study demonstrated that miR-186 regulates the chemoresistance of NSCLC cells by modulating the MAPT expression level both in vitro and in vivo. miR-186 may represent a new therapeutic target for the improvement of the clinical outcome in NSCLC.
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http://dx.doi.org/10.1039/c6mb00576dDOI Listing
October 2016

Poly (C)-binding protein 2 (PCBP2) promotes the progression of esophageal squamous cell carcinoma (ESCC) through regulating cellular proliferation and apoptosis.

Pathol Res Pract 2016 Aug 27;212(8):717-25. Epub 2016 May 27.

School of Public Health, Nanjing Medical University, 101 Longmian Road, Jiangning District, Nanjing 210000, Jiangsu, China. Electronic address:

PCBP2 (Poly(C)-binding protein 2) is a member of PCBP family, which has many functions including mRNA stabilization, translational silence and translational enhancement performed by their poly(C)-binding ability. The abnormal expression of PCBP2 was correlated with various carcinomas. However, the significance and mechanism of PCBP2 in esophageal squamous cell carcinoma (ESCC) progression remain unclear. In this study, Western Blot and immunohistochemistry (IHC) analysis revealed that PCBP2 was overexpressed in ESCC tissues and cell lines. Statistical results also indicated that PCBP2 expression level was significantly positively correlated with ESCC clinicopathological parameters such as tumor grade and tumor size. Furthermore, PCBP2 expression level could also be recognized as an independent prognostic factor for ESCC patients' overall survival. Serum starvation and refeeding assay along with PCBP2-shRNA transfection demonstrated that PCBP2 expression promoted proliferation of ESCC cells. The results above are partly due to growth arrest of cell cycle at G1/S phase. We also found that reduced PCBP2 expression might induce ESCC cell apoptosis with increased cleaved caspase3 expression. Overall, our findings indicated that PCBP2 might be involved in the ESCC progression and be considered as a new treatment target in ESCC.
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http://dx.doi.org/10.1016/j.prp.2016.05.008DOI Listing
August 2016

Overexpression of Dishevelled-2 contributes to proliferation and migration of human esophageal squamous cell carcinoma.

J Mol Histol 2016 Jun 15;47(3):287-95. Epub 2016 Apr 15.

Department of Chemotherapy, Jiangsu Cancer Hospital Affiliated to Nanjing Medical University, 42 Baiziting Raod, Nanjing, 210000, Jiangsu, China.

Dishevelled-2 (Dvl2) was associated with tumor cell proliferation and migration. We aimed to examine the mechanism of Dvl2 in esophageal squamous cell carcinoma (ESCC). Dvl2 was overexpressed in human ESCC tissues and cell lines ECA109 and TE1 cells. CCK-8 and colony formation assay was performed to evaluate the proliferation in ECA109 cells transfected with Dvl2-shRNA. Wound-healing assay and transwell assay were used to examine the activities of migration and invasion in Dvl2-silenced ESCC cells. Knockdown of Dvl2 significantly reduced ECA109 cell proliferation and migration. Moreover, we demonstrated that the proliferation and migration ability of Dvl2 might through the activation of Wnt pathway by targeting the Cyclin D1 and MMP-9. We came to the conclusion that the proliferation and migration effects of Dvl2 might contribute to malignant development of human ESCC.
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http://dx.doi.org/10.1007/s10735-016-9674-3DOI Listing
June 2016

Antiproliferative effects and molecular mechanisms of troglitazone in human cervical cancer in vitro.

Onco Targets Ther 2015 26;8:1211-8. Epub 2015 May 26.

Department of Radiotherapy, Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, People's Republic of China.

We investigated the effects of troglitazone on human cervical cancer SiHa cells and its mechanisms of action. SiHa cells were incubated with different concentrations of troglitazone (100, 200, or 400 μg/mL) for 24, 48, and 72 hours. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) assay; cell cycle and apoptosis were detected by flow cytometry; and morphology of SiHa cells was observed under an inverted microscope. pcDNA3.1 and pcDNA3.1-Skp2 plasmids were constructed and then transfected into SiHa cells. Protein expression was analyzed by Western blotting. Troglitazone inhibited the proliferation of SiHa cells in a time- and concentration-dependent manner. Troglitazone caused G0/1 phase arrest but failed to reduce apoptosis in SiHa cells. Troglitazone significantly increased expression of p27 but decreased Skp2 expression. Skp2 overexpression inhibited the role of troglitazone in increasing expression of p27, and the cell cycle inhibitory effect of troglitazone. Troglitazone can inhibit SiHa cell viability by affecting cell cycle distribution but not apoptosis, and Skp2 and p27 may play a critical role.
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http://dx.doi.org/10.2147/OTT.S79899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4454221PMC
June 2015

Radiosensitization effect of nedaplatin on nasopharyngeal carcinoma cells in different status of Epstein-Barr virus infection.

Biomed Res Int 2014 12;2014:713674. Epub 2014 May 12.

Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing 210009, China.

This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0-100 μg/mL nedaplatin, and inhibitory effects on cell viability and IC50 were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50 values of 34.32 and 63.69 μg/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.
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http://dx.doi.org/10.1155/2014/713674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036599PMC
January 2015
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