Publications by authors named "Da Fu"

136 Publications

MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211041191

Shanghai Tenth People's Hospital, 278245Tongji University School of Medicine, Shanghai, China.

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.
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http://dx.doi.org/10.1177/15330338211041191DOI Listing
September 2021

New Insights into the Role of NLRP3 Inflammasome in Pathogenesis and Treatment of Chronic Obstructive Pulmonary Disease.

J Inflamm Res 2021 26;14:4155-4168. Epub 2021 Aug 26.

Department of Immunology, School of Medicine, Nantong University, Nantong, Jiangsu, 226019, People's Republic of China.

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by chronic airway obstruction and emphysema. Accumulating studies have shown that the onset and development of COPD are related to an aberrant immune response induced by the dysregulation of a number of genetic and environmental factors, while the exact pathogenesis of this disease is not well defined. Emerging studies based on tests on samples from COPD patients, animal models, pharmacological and genetic data suggest that the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation is required in the lung inflammatory responses in the development of COPD. Although the available clinical studies targeting the inflammasome effector cytokine, IL-1β, or IL-1 signaling do not show positive outcomes for COPD treatment, many alternative strategies have been proposed by recent emerging studies. Here, we highlight the recent progress in our understanding of the role of the NLRP3 inflammasome in COPD and propose possible future studies that may further elucidate the roles of the inflammasome in the pathogenesis or the intervention of this inflammatory lung disease.
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http://dx.doi.org/10.2147/JIR.S324323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405160PMC
August 2021

Exosomal microRNA-15a from mesenchymal stem cells impedes hepatocellular carcinoma progression via downregulation of SALL4.

Cell Death Discov 2021 Aug 28;7(1):224. Epub 2021 Aug 28.

Department of Radiology, The Fourth Affiliated Hospital of Anhui Medical University, 230012, Hefei, China.

Hepatocellular carcinoma (HCC) is a heterogeneous tumor with an increased incidence worldwide accompanied by high mortality and dismal prognosis. Emerging evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes possess protective effects against various human diseases by transporting microRNAs (miRNAs or miRs). We aimed to explore the role of exosomal miR-15a derived from MSCs and its related mechanisms in HCC. Exosomes were isolated from transduced MSCs and co-incubated with Hep3B and Huh7 cells. miR-15a expression was examined by RT-qPCR in HCC cells, MSCs, and secreted exosomes. CCK-8, transwell, and flow cytometry were used to detect the effects of miR-15a or spalt-like transcription factor 4 (SALL4) on cell proliferative, migrating, invasive, and apoptotic properties. A dual-luciferase reporter gene assay was performed to validate the predicted targeting relationship of miR-15a with SALL4. Finally, in vivo experiments in nude mice were implemented to assess the impact of exosome-delivered miR-15a on HCC. The exosomes from MSCs restrained HCC cell proliferative, migrating, and invasive potentials, and accelerated their apoptosis. miR-15a was expressed at low levels in HCC cells and could bind to SALL4, thus curtailing the proliferative, migrating, and invasive abilities of HCC cells. Exosomes successfully delivered miR-15a to HCC cells. Exosomal miR-15a depressed tumorigenicity and metastasis of HCC tumors in vivo. Overall, exosomal miR-15a from MSCs can downregulate SALL4 expression and thereby retard HCC development.
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http://dx.doi.org/10.1038/s41420-021-00611-zDOI Listing
August 2021

The power and the promise of circRNAs for cancer precision medicine with functional diagnostics and prognostic prediction.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.

Circular RNA (circRNA) is a large class of covalently closed circular RNA. As a member of competitive endogenous RNA (ceRNA), it participates in the regulation of circRNA-miRNA-mRNA network and plays an important role in the regulation of physiology and pathology. CircRNA is produced by the reverse splicing of exon, intron or both, forming exon or intron circRNA. Studies have shown that circRNA is a ubiquitous molecule, which exceeds the linear mRNA distributed in human cells. Because of its covalent closed-loop structure, circRNA is resistant to RNase R, which is more stable than linear mRNA; circRNA is highly conserved in different species. It was found that circRNA competitively adsorbs miRNA, as a miRNA sponge, to involve in the expression regulation of a variety of genes and plays an important role in tumor development, invasion, metastasis and other processes. These molecules offer new potential opportunities for therapeutic intervention and serve as biomarkers for diagnosis. In this paper, the origin, characteristics and functions of circRNA and its role in tumor development, invasion and metastasis, diagnosis and prognosis are reviewed.
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http://dx.doi.org/10.1093/carcin/bgab071DOI Listing
July 2021

Basic approaches, challenges and opportunities for the discovery of small molecule anti-tumor drugs.

Am J Cancer Res 2021 15;11(6):2386-2400. Epub 2021 Jun 15.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology Changsha 410004, Hunan, China.

Chemotherapy is one of the main treatments for cancer, especially for advanced cancer patients. In the past decade, significant progress has been made with the research into the molecular mechanisms of cancer cells and the precision medicine. The treatment on cancer patients has gradually changed from cytotoxic chemotherapy to precise treatment strategy. Research into anticancer drugs has also changed from killing effects on all cells to targeting drugs for target genes. Besides, researchers have developed the understanding of the abnormal physiological function, related genomics, epigenetics, and proteomics of cancer cells with cancer genome sequencing, epigenetic research, and proteomic research. These technologies and related research have accelerated the development of related cancer drugs. In this review, we summarize the research progress of anticancer drugs, the current challenges, and future opportunities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263657PMC
June 2021

Protein disulfide isomerase inhibits endoplasmic reticulum stress response and apoptosis via its oxidoreductase activity in colorectal cancer.

Cell Signal 2021 Oct 7;86:110076. Epub 2021 Jul 7.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address:

Protein disulfide isomerase (PDI), a principal endoplasmic reticulum resident oxidoreductase chaperone, is known to play a role in malignancies. This study aims to explore the molecular mechanism by which PDI regulates endoplasmic reticulum stress and the apoptosis signaling pathway in colorectal cancer (CRC). We determined the expression of PDI in CRC tissues and adjacent normal tissues. Gain- and loss- of function assays were conducted to evaluate the effects of PDI on oxidative stress, endoplasmic reticulum stress, and apoptosis in CRC cells, as reflected by hydrogen peroxide (HO) level and the expression of related proteins. PDI protein expression was upregulated in CRC tissues. Small molecule inhibitor of PDI or PDI knockdown reduced CRC cell viability and induced apoptosis. Overexpression of wild-type PDI augmented the viability of CRC cells and inhibited endoplasmic reticulum stress response and apoptosis. Small molecule inhibitor of PDI or PDI knockdown increased intracellular HO level and activated apoptosis signaling pathway, which could be reversed by wild-type PDI restoration. Moreover, the catalytic active site of C-terminal of PDI was found to be indispensable for the regulatory effects of PDI on HO levels, apoptosis and cell viability in CRC cells. Collectively, PDI inhibits endoplasmic reticulum stress and apoptosis of CRC cells through its oxidoreductase activity, thereby promoting the malignancy of CRC.
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http://dx.doi.org/10.1016/j.cellsig.2021.110076DOI Listing
October 2021

A miR-212-3p/SLC6A1 Regulatory Sub-Network for the Prognosis of Hepatocellular Carcinoma.

Cancer Manag Res 2021 28;13:5063-5075. Epub 2021 Jun 28.

Department of Pathology, Shihezi University School of Medicine, Shihezi, Xinjiang, 832002, People's Republic of China.

Introduction: Hepatocellular carcinoma (HCC) is a liver cancer with a poor prognosis. Owing to the complexity and limited pathogenic mechanism research on HCC, the molecular targeted therapy has been hindered.

Methods: In this study, we categorized transcriptome data into low-Myc and high-Myc expression groups in 365 HCC samples, screened the differentially expressed RNAs, including 441 DE-lncRNAs, 99 DE-miRNAs and 612 DE-mRNAs, constructed a lncRNA-miRNA-mRNA regulatory network, and selected a hub triple regulatory network through cytoHubba analysis. Through Gene ontology and KEGG pathway, a hub regulatory network was particularly enriched in the "Wnt signaling pathway" and "Cytochrome P450-arranged by substrate type" by Metascape. The prognostic genes in the hub regulatory network were evaluated by the RNA expression analysis, Kaplan-Meier (KM) survival analysis, and correlation analysis.

Results: The results showed that miR-212-3p/SLC6A1 axis was a potential prognostic model for HCC. Furthermore, IHC analysis showed down-regulated expression of SLC6A1 in HCC tissues and Alb-Cre;Myc mouse liver cancer tissues. The genetics and epigenetic analysis indicated that SLC6A1 expression was negatively correlated with DNA methylation. Immune infiltration analysis showed a negative relation between SLC6A1 and T cell exhaustion/monocyte in liver cancer tissues.

Conclusion: In summary, the study revealed that miR-212-3p/SLC6A1 axis could serve as a crucial therapeutic target for HCC.
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http://dx.doi.org/10.2147/CMAR.S308986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254378PMC
June 2021

Construction of a Myc-associated ceRNA network reveals a prognostic signature in hepatocellular carcinoma.

Mol Ther Nucleic Acids 2021 Jun 1;24:1033-1050. Epub 2021 May 1.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Hepatocellular carcinoma (HCC) remains an extremely lethal disease worldwide. High-throughput methods have revealed global transcriptome dysregulation; however, a comprehensive investigation of the complexity and behavioral characteristics of the competing endogenous RNA (ceRNA) network in HCC is lacking. In this study, we extracted the transcriptome (RNA) sequencing data of 371 HCC patients from The Cancer Genome Atlas platform. With the comparison of the high Myc expression (Myc) tumor and low Myc expression (Myc) tumor groups in HCC, we identified 1,125 differentially expressed (DE) mRNAs, 589 long non-coding RNAs (lncRNAs), and 93 microRNAs (miRNAs). DE RNAs predicted the interactions necessary to construct an associated Myc ceRNA network, including 19 DE lncRNAs, 5 miRNAs, and 72 mRNAs. We identified a significant signature (long intergenic non-protein-coding [LINC] RNA 2691 [LINC02691] and LINC02499) that effectively predicted overall survival and had protective effects. The target genes of microRNA (miR)-212-3p predicted to intersect with DE mRNAs included SEC14-like protein 2 (SEC14L2) and solute carrier family 6 member 1 (SLC6A1), which were strongly correlated with survival and prognosis. With the use of the lncRNA-miRNA-mRNA axis, we constructed a ceRNA network containing four lncRNAs (LINC02691, LINC02499, LINC01354, and NAV2 antisense RNA 4), one miRNA (miR-212-3p), and two mRNAs (SEC14L2 and SLC6A1). Overall, we successfully constructed a mutually regulated ceRNA network and identified potential precision-targeted therapies and prognostic biomarkers.
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http://dx.doi.org/10.1016/j.omtn.2021.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167205PMC
June 2021

Quantitative proteomics characterization of cancer biomarkers and treatment.

Mol Ther Oncolytics 2021 Jun 20;21:255-263. Epub 2021 Apr 20.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.

Cancer accounted for 16% of all death worldwide in 2018. Significant progress has been made in understanding tumor occurrence, progression, diagnosis, treatment, and prognosis at the molecular level. However, genomics changes cannot truly reflect the state of protein activity in the body due to the poor correlation between genes and proteins. Quantitative proteomics, capable of quantifying the relatively different protein abundance in cancer patients, has been increasingly adopted in cancer research. Quantitative proteomics has great application potentials, including cancer diagnosis, personalized therapeutic drug selection, real-time therapeutic effects and toxicity evaluation, prognosis and drug resistance evaluation, and new therapeutic target discovery. In this review, the development, testing samples, and detection methods of quantitative proteomics are introduced. The biomarkers identified by quantitative proteomics for clinical diagnosis, prognosis, and drug resistance are reviewed. The challenges and prospects of quantitative proteomics for personalized medicine are also discussed.
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http://dx.doi.org/10.1016/j.omto.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142045PMC
June 2021

The power and the promise of organoid models for cancer precision medicine with next-generation functional diagnostics and pharmaceutical exploitation.

Transl Oncol 2021 Aug 18;14(8):101126. Epub 2021 May 18.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China; Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Radiology, The Forth Affiliated Hospital of Anhui Medical University, Hefei 230012, China. Electronic address:

As organ-specific three-dimensional cell clusters derived from cancer tissue or cancer-specific stem cells, cancer-derived organoids are organized in the same manner of the cell sorting and spatial lineage restriction in vivo, making them ideal for simulating the characteristics of cancer and the heterogeneity of cancer cells in vivo. Besides the applications as a new in vitro model to study the physiological characteristics of normal tissues and organs, organoids are also used for in vivo cancer cell characterization, anti-cancer drug screening, and precision medicine. However, organoid cultures are not without limitations, i.e., the lack of nerves, blood vessels, and immune cells. As a result, organoids could not fully replicate the characteristics of organs but partially simulate the disease process. This review attempts to provide insights into the organoid models for cancer precision medicine.
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http://dx.doi.org/10.1016/j.tranon.2021.101126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144479PMC
August 2021

MicroRNA-499 serves as a sensitizer for lung cancer cells to radiotherapy by inhibition of CK2α-mediated phosphorylation of p65.

Mol Ther Oncolytics 2021 Jun 3;21:171-182. Epub 2021 Apr 3.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

The present study aimed to define the tumor-suppressive role of microRNA-499 (miR-499) in lung cancer cells and its underlying mechanism. First, qRT-PCR analysis revealed poor expression of miR-499 in clinical samples and cell lines of lung cancer. Next, we performed loss- and gain-of-function experiments for the expression of miR-499 in lung cancer cells exposed to irradiation (IR) to determine the effect of miR-499 expression on cell viability and apoptosis as well as tumor growth. Results showed that overexpression of miR-499 inhibited cell viability, enhanced the radiosensitivity of lung cancer cells, and promoted cell apoptosis under IR. Furthermore, CK2α was verified to be a target of miR-499, and miR-499 was identified to repress p65 phosphorylation by downregulating CK2α expression, which ultimately diminished the survival rate of lung cancer cells under IR. Collectively, the key findings of the study illustrate the tumor-inhibiting function of miR-499 and confirmed that miR-499-mediated CK2α inhibition and altered p65 phosphorylation enhances the sensitivity of lung cancer cells to IR.
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http://dx.doi.org/10.1016/j.omto.2021.03.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099482PMC
June 2021

microRNA-873 inhibits self-renewal and proliferation of pancreatic cancer stem cells through pleckstrin-2-dependent PI3K/AKT pathway.

Cell Signal 2021 Aug 27;84:110025. Epub 2021 Apr 27.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tenth People's Hospital of Tongji University, Shanghai 200072, China. Electronic address:

Recent studies have emphasized microRNAs (miRs) as crucial regulators in the occurrence and development of pancreatic cancer that continues to be one of the deadliest malignancies with few effective therapies. The study aimed to investigate the functional role of miR-873 and its associated mechanism to unravel the biological characteristics of pancreatic cancer stem cells in tumor growth. The expression patterns of pleckstrin-2 (PLEK2) and miR-873 were detected in the pancreatic cancer tissues. Then to further investigate specific role of miR-873, the pancreatic cancer stem cells were treated with miR-873 mimic, PLEK2, small interfering RNA against PLEK2, LY294002 (inhibitor of phosphatidylinositol 3-kinase/protein kinase B [PI3K/AKT] pathway) to detect the relative gene expression as well as their effects on cell self-renewal, proliferation and apoptosis. Finally, the tumor formation in nude mice was measured to verify the preceding results in vivo. Pancreatic cancer tissues exhibited a decline of miR-873 expression and an enhancement of PLEK2 expression. miR-873 targeted PLEK2 and downregulated its expression, leading to inhibition of PI3K/AKT pathway. Overexpressed miR-873 or silenced PLEK2 inhibited the self-renewal and proliferation while promoting the apoptosis of pancreatic cancer stem cells. Tumor formation was inhibited by overexpressed miR-873 or silenced PLEK2 in nude mice. Overall, miR-873 can suppress the self-renewal and proliferation of pancreatic cancer stem cells by blocking PLEK2-dependent PI3K/AKT pathway. Hence, this study contributes to understanding the role of miR-873 in pancreatic cancer stem cells and its underlying molecular mechanisms to aid in the development of effective pancreatic cancer therapeutics.
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http://dx.doi.org/10.1016/j.cellsig.2021.110025DOI Listing
August 2021

Paving the way for small-molecule drug discovery.

Am J Transl Res 2021 15;13(3):853-870. Epub 2021 Mar 15.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins, which have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. As commonly used medications, small-molecule drugs can be taken orally, which enter cells to act on intracellular targets. These characteristics make small-molecule drugs promising candidates for drug development, and they are increasingly favored in the pharmaceutical market. Despite the advancements in molecular genetics and effective new processes in drug development, the drugs currently used in clinical practice are inadequate due to their poor efficacy or severe side effects. Therefore, developing new safe and efficient drugs is a top priority for disease control and curing.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014367PMC
March 2021

MicroRNA-497-5p Is Downregulated in Hepatocellular Carcinoma and Associated with Tumorigenesis and Poor Prognosis in Patients.

Int J Genomics 2021 16;2021:6670390. Epub 2021 Mar 16.

Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China.

Background: MicroRNAs (miRNAs) have been demonstrated to exhibit important regulatory roles in multiple malignancies, including hepatocellular carcinoma (HCC). hsa-miR-497-5p was reported to involve in cancer progression and poor prognosis in many kinds of tumors. However, the expression and its clinical significance of hsa-miR-497-5p in HCC remain unclear.

Methods: In the present study, we investigated the expression of hsa-miR-497-5p in HCC and analyzed the correction of clinical features with prognosis. The expression levels of hsa-miR-497-5p and potential target genes were analyzed in HCC and adjacent noncancerous tissues using The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze hsa-miR-497-5p levels in 328 HCC tissues and 30 paired adjacent noncancer tissues. Overall survival (OS) and progression-free survival (PFS) of patients with HCC were assessed using the Kaplan-Meier method and the log-rank test.

Results: The hsa-miR-497-5p expression levels were decreased, and its target genes ACTG1, CSNK1D, PPP1CC, and BIRC5 were upregulated in HCC tissues compared with normal tissues. Lower levels of hsa-miR-497-5p expression and higher levels of the four target genes were significantly associated with higher tumor diameter. Moreover, patients with lower hsa-miR-497-5p expression and higher target genes levels had shorter OS.

Conclusion: The expression levels of hsa-miR-497-5p may play an important regulatory role in HCC and are closely correlated with HCC progression and poor prognosis in patients. The hsa-miR-497-5p may be a specific therapeutic target for the treatment of HCC.
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http://dx.doi.org/10.1155/2021/6670390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987441PMC
March 2021

microRNA-320b suppresses HNF4G and IGF2BP2 expression to inhibit angiogenesis and tumor growth of lung cancer.

Carcinogenesis 2021 May;42(5):762-771

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, P.R. China.

We examined the effect of microRNA-320b (miR-320b) on tumor growth and angiogenesis in lung cancer and also determined its downstream molecular mechanisms. Lung cancer tissues and adjacent non-cancerous tissues were collected from 66 patients with lung cancer. miR-320b expression was experimentally determined to be expressed at low level in cancer tissues. The results of gain-of-function experiments suggested that miR-320b overexpression suppressed cancer cell invasion, tube formation, tumor volume and angiogenesis in xenografted nude mice. Hepatocyte nuclear factor 4 gamma (HNF4G) was identified as a target of miR-320b based on in silico analysis. Dual-luciferase reporter gene assays further identified the binding relationship between HNF4G and miR-320b. Lung cancer tissues exhibited increased expression of HNF4G and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Meanwhile, HNF4G knockdown suppressed IGF2BP2 expression, thereby repressing cancer cell invasion and tube formation. Furthermore, IGF2BP2 modified m6A to increase the expression of thymidine kinase 1 (TK1), thus promoting angiogenesis. In nude mice, restoration of TK1 reversed the suppressive effect of miR-320b overexpression on tumor growth rate and CD31 expression. In conclusion, miR-320b suppresses lung cancer growth and angiogenesis by inhibiting HNF4G, IGF2BP2 and TK1.
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http://dx.doi.org/10.1093/carcin/bgab023DOI Listing
May 2021

M2 macrophage-derived exosomal microRNA-155-5p promotes the immune escape of colon cancer by downregulating ZC3H12B.

Mol Ther Oncolytics 2021 Mar 6;20:484-498. Epub 2021 Feb 6.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.

Previous evidence has highlighted M2 macrophage regulation of cancer cells via exosome shuttling of microRNAs (miRNAs or miRs). The current study set out to explore the possible role of M2 macrophage-derived exosomal miR-155-5p in regard to immune escape of colon cancer cells. Experimental data from quantitative reverse-transcriptase PCR (qRT-PCR) and western blot analysis revealed highly expressed miR-155-5p and interleukin (IL)-6 and poorly expressed ZC3H12B in M2 macrophage-derived exosomes. Additionally, miR-155-5p could be transferred by M2 macrophage-isolated exosomes to colon cancer cells, which targeted ZC3H12B by binding to the 3¢ UTR, as identified by dual luciferase reporter gene. Meanwhile, gain- and loss-of function experimentation on miR-155-5p and ZC3H12B in SW48 and HT29 cells cocultured with M2 macrophage-secreted exosomes demonstrated that miR-155-5p overexpression or ZC3H12B silencing promoted the proliferation and antiapoptosis ability of SW48 and HT29 cells, as well as augmenting the CD3 T cell proliferation and the proportion of interferon (IFN)-γ T cells. Xenograft models confirmed that M2 macrophage-derived exosomal miR-155-5p reduced the ZC3H12B expression to upregulate IL-6, which consequently induced immune escape and tumor formation. Collectively, our findings indicated that M2 macrophage-derived exosomal miR-155-5p can potentially promote the immune escape of colon cancer by impairing ZC3H12B-mediated IL-6 stability reduction, thereby promoting the occurrence and development of colon cancer.
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http://dx.doi.org/10.1016/j.omto.2021.02.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932913PMC
March 2021

KDM5A silencing transcriptionally suppresses the FXYD3-PI3K/AKT axis to inhibit angiogenesis in hepatocellular cancer via miR-433 up-regulation.

J Cell Mol Med 2021 04 23;25(8):4040-4052. Epub 2021 Feb 23.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

Hepatocellular cancer (HCC) has been reported to belong to one of the highly vascularized solid tumours accompanied with angiogenesis of human umbilical vein endothelial cells (HUVECs). KDM5A, an attractive drug target, plays a critical role in diverse physiological processes. Thus, this study aims to investigate its role in angiogenesis and underlying mechanisms in HCC. ChIP-qPCR was utilized to validate enrichment of H3K4me3 and KDM5A on the promotor region of miR-433, while dual luciferase assay was carried out to confirm the targeting relationship between miR-433 and FXYD3. Scratch assay, transwell assay, Edu assay, pseudo-tube formation assay and mice with xenografted tumours were conducted to investigate the physiological function of KDM5A-miR-433-FXYD3-PI3K-AKT axis in the progression of HCC after loss- and gain-function assays. KDM5A p-p85 and p-AKT were highly expressed but miR-433 was down-regulated in HCC tissues and cell lines. Depletion of KDM5A led to reduced migrative, invasive and proliferative capacities in HCC cells, including growth and a lowered HUVEC angiogenic capacity in vitro. Furthermore, KDM5A suppressed the expression of miR-433 by demethylating H3K4me3 on its promoterregion. miR-433 negatively targeted FXYD3. Depleting miR-433 or re-expressing FXYD3 restores the reduced migrative, invasive and proliferative capacities, and lowers the HUVEC angiogenic capacity caused by silencing KDM5A. Therefore, KDM5A silencing significantly suppresses HCC tumorigenesis in vivo, accompanied with down-regulated miR-433 and up-regulated FXYD3-PI3K-AKT axis in tumour tissues. Lastly, KDM5A activates the FXYD3-PI3K-AKT axis to enhance angiogenesis in HCC by suppressing miR-433.
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http://dx.doi.org/10.1111/jcmm.16371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051710PMC
April 2021

Cancer-associated fibroblast-derived exosomal microRNA-24-3p enhances colon cancer cell resistance to MTX by down-regulating CDX2/HEPH axis.

J Cell Mol Med 2021 04 23;25(8):3699-3713. Epub 2021 Feb 23.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

MicroRNA-24-3p (miR-24-3p) has been implicated as a key promoter of chemotherapy resistance in numerous cancers. Meanwhile, cancer-associated fibroblasts (CAFs) can secret exosomes to transfer miRNAs, which mediate tumour development. However, little is known regarding the molecular mechanism of CAF-derived exosomal miR-24-3p in colon cancer (CC). Hence, this study intended to characterize the functional relevance of CAF-derived exosomal miR-24-3p in CC cell resistance to methotrexate (MTX). We identified differentially expressed HEPH, CDX2 and miR-24-3p in CC through bioinformatics analyses, and validated their expression in CC tissues and cells. The relationship among HEPH, CDX2 and miR-24-3p was verified using ChIP and dual-luciferase reporter gene assays. Exosomes were isolated from miR-24-3p inhibitor-treated CAFs (CAFs-exo/miR-24-3p inhibitor), which were used in combination with gain-of-function and loss-of-function experiments and MTX treatment. CCK-8, flow cytometry and colony formation assays were conducted to determine cell viability, apoptosis and colony formation, respectively. Based on the findings, CC tissues and cells presented with high expression of miR-24-3p and low expression of HEPH and CDX2. CDX2 was a target gene of miR-24-3p and could up-regulate HEPH. Under MTX treatment, overexpressed CDX2 or HEPH and down-regulated miR-24-3p reduced cell viability and colony formation and elevated cell apoptosis. Furthermore, miR-24-3p was transferred into CC cells via CAF-derived exosomes. CAF-derived exosomal miR-24-3p inhibitor diminished cell viability and colony formation and increased cell apoptosis in vitro and inhibited tumour growth in vivo under MTX treatment. Altogether, CAF-derived exosomal miR-24-3p accelerated resistance of CC cells to MTX by down-regulating CDX2/HEPH axis.
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http://dx.doi.org/10.1111/jcmm.15765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051723PMC
April 2021

Identification of Potential BRAF Inhibitor Joint Therapy Targets in PTC based on WGCAN and DCGA.

J Cancer 2021 21;12(6):1779-1791. Epub 2021 Jan 21.

Shanghai Center for Thyroid Disease, Shanghai Tenth People's Hospital, Shanghai, China.

As the most common mutation in papillary thyroid cancer (PTC), B-type Raf kinase V600E mutation ( ) has become an important target for the clinical treatment of PTC. However, the clinical application still faces the problem of resistance to BRAF inhibitors (BRAFi). Therefore, exploring BRAF-associated prognostic factors to providing potential joint targets is important for combined targeted therapy with BRAFi. In this study, we combined transcript data and clinical information from 199 wild-type ( ) patients and 283 mutant patients collected from The Cancer Genome Atlas (TCGA), and screened 455 BRAF- associated genes through differential analysis and weighted gene co-expression network analysis. Based on these -associated genes, we performed functional enrichment analysis and co-expression differential analysis and constructed a core co-expression network. Next, genes in the differential co-expression network were used to predict drugs for therapy in the crowd extracted expression of differential signatures (CREEDS) database, and the key genes were selected based on the hub co-expression network through survival analyses and receiver operating characteristic (ROC) curve analyses. Finally, we obtained eight BRAF -associated biomarkers with both prognostic and diagnostic values as potential BRAFi joint targets, including , , , , , , , and . Among these genes, FN1, MET, PROS1, and were validated through GEO database. Two novel biomarkers, PROS1 and , were further validated by qRT-PCR experiment. Besides, we obtained four potential targeted drugs that could be used in combination with BRAFi to treat PTC, including MET inhibitor, ERBB3 inhibitor, anti-NaPi2b antibody-drug conjugate, and carboplatin through literature review. The study provided potential drug targets for combination therapy with BRAFi for PTC to overcome the drug resistance for BRAFi.
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http://dx.doi.org/10.7150/jca.51551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890315PMC
January 2021

Biosafety risk assessment of nanoparticles: Evidence from food case studies.

Environ Pollut 2021 Apr 4;275:116662. Epub 2021 Feb 4.

National Engineering Laboratory for Deep Process of Rice and Byproducts, Hunan Province Key Laboratory of Edible Forestry Resources Safety and Processing Utilization, Hunan Key Laboratory of Processed Food for Special Medical Purpose, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, 410004, Hunan, China.

Nanotechnology provides a wide range of benefits in the food industry in improving food tastes, textures, sensations, quality, shelf life, and food safety. Recently, potential adverse effects such as toxicity and safety concerns have been associated with the increasing use of engineered nanoparticles in food industry. Additionally, very limited information is known concerning the behavior, properties and effects of food nano-materials in the gastrointestinal tract. There is explores the current advances and provides insights of the potential risks of nanoparticles in the food industry. Specifically, characteristics of food nanoparticles and their absorption in the gastrointestinal tract, the effects of food nanoparticles against the gastrointestinal microflora, and the potential toxicity mechanisms in different organs and body systems are discussed. This review would provide references for further investigation of nano-materials toxicity effect in foods and their molecular mechanisms. It will help to develop safer foods and expand nano-materials applications in safe manner.
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http://dx.doi.org/10.1016/j.envpol.2021.116662DOI Listing
April 2021

Comprehensive analysis to identify DLEU2L/TAOK1 axis as a prognostic biomarker in hepatocellular carcinoma.

Mol Ther Nucleic Acids 2021 Mar 1;23:702-718. Epub 2021 Jan 1.

National Engineering Laboratory for Deep Process of Rice and Byproducts, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, Hunan, China.

Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors that are harmful to human health. Increasing evidence has underscored the critical role of the competitive endogenous RNA (ceRNA) regulatory networks among various human cancers. However, the complexity and behavior characteristics of the ceRNA network in HCC were still unclear. In this study, we aimed to clarify a phosphatase and tensin homolog (PTEN)-related ceRNA regulatory network and identify potential prognostic markers associated with HCC. The expression profiles of three RNAs (long non-coding RNAs [lncRNAs], microRNAs [miRNAs], and mRNAs) were extracted from The Cancer Genome Atlas (TCGA) database. The DLEU2L-hsa-miR-100-5p/ hsa-miR-99a-5p-TAOK1 ceRNA network related to the prognosis of HCC was obtained by performing bioinformatics analysis. Importantly, we identified the DLEU2L/TAOK1 axis in the ceRNA by using correlation analysis, and it appeared to become a clinical prognostic model by Cox regression analysis. Furthermore, methylation analyses suggested that the abnormal upregulation of the DLEU2L/TAOK1 axis likely resulted from hypomethylation, and immune infiltration analysis showed that the DLEU2L/TAOK1 axis may have an impact on the changes in the tumor immune microenvironment and the development of HCC. In summary, the current study constructing a ceRNA-based DLEU2L/TAOK1 axis might be a novel important prognostic factor associated with the diagnosis and prognosis of HCC.
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http://dx.doi.org/10.1016/j.omtn.2020.12.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851426PMC
March 2021

Unravelling the Role of LncRNA WT1-AS/miR-206/NAMPT Axis as Prognostic Biomarkers in Lung Adenocarcinoma.

Biomolecules 2021 02 2;11(2). Epub 2021 Feb 2.

College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha 410004, China.

Lung cancer is the world's highest morbidity and mortality of malignant tumors, with lung adenocarcinoma (LUAD) as a major subtype. The competitive endogenous RNA (ceRNA) regulative network provides opportunities to understand the relationships among different molecules, as well as the regulative mechanisms among them in order to investigate the whole transcriptome landscape in cancer pathology. We designed this work to explore the role of a key oncogene, MYC, in the pathogenesis of LUAD, and this study aims to identify important long noncoding RNA (lncRNA)-microRNA (miRNA)- transcription factor (TF) interactions in non-small cell lung cancer (NSCLC) using a bioinformatics analysis. The Cancer Genome Atlas (TCGA) database, containing mRNA expression data of NSCLC, was used to determine the deferentially expressed genes (DEGs), and the ceRNA network was composed of WT1-AS, miR-206, and nicotinamide phosphoribosyltransferase (NAMPT) bashing on the MYC expression level. The Kaplan-Meier univariate survival analysis showed that these components may be closely related prognostic biomarkers and will become new ideas for NSCLC treatment. Moreover, the high expression of WT1-AS and NAMPT and low expression of miR-206 were associated with a shortened survival in NSCLC patients, which provided a survival advantage. In summary, the current study constructing a ceRNA-based WT1-AS/miR-206/NAMPT axis might be a novel important prognostic factor associated with the diagnosis and prognosis of LUAD.
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http://dx.doi.org/10.3390/biom11020203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912827PMC
February 2021

Systematic analysis using a bioinformatics strategy identifies SFTA1P and LINC00519 as potential prognostic biomarkers for lung squamous cell carcinoma.

Am J Transl Res 2021 15;13(1):168-182. Epub 2021 Jan 15.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai 200072, China.

Lung cancer has high incidence and mortality rates, in which lung squamous cell carcinoma (LUSC) is a primary type of non-small cell lung carcinoma (NSCLC). The aim of our study was to discover long non-coding RNAs (lncRNAs) associated with diagnose and prognosis for LUSC. RNA sequencing data obtained from LUSC samples were extracted from The Cancer Genome Atlas database (TCGA). Two prognosis-associated lncRNAs (including SFTA1P and LINC00519) were selected from LUSC samples, and the expression levels were also verified to be associated abnormal in LUSC clinical samples. Our findings demonstrate that lncRNAs SFTA1P and LINC00519 exert important functions in human LUSC and may serve as new targets for LUSC diagnosis and therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847518PMC
January 2021

Identified GNGT1 and NMU as Combined Diagnosis Biomarker of Non-Small-Cell Lung Cancer Utilizing Bioinformatics and Logistic Regression.

Dis Markers 2021 6;2021:6696198. Epub 2021 Jan 6.

Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.

Non-small-cell lung cancer (NSCLC) is one of the most devastating diseases worldwide. The study is aimed at identifying reliable prognostic biomarkers and to improve understanding of cancer initiation and progression mechanisms. RNA-Seq data were downloaded from The Cancer Genome Atlas (TCGA) database. Subsequently, comprehensive bioinformatics analysis incorporating gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the protein-protein interaction (PPI) network was conducted to identify differentially expressed genes (DEGs) closely associated with NSCLC. Eight hub genes were screened out using Molecular Complex Detection (MCODE) and cytoHubba. The prognostic and diagnostic values of the hub genes were further confirmed by survival analysis and receiver operating characteristic (ROC) curve analysis. Hub genes were validated by other datasets, such as the Oncomine, Human Protein Atlas, and cBioPortal databases. Ultimately, logistic regression analysis was conducted to evaluate the diagnostic potential of the two identified biomarkers. Screening removed 1,411 DEGs, including 1,362 upregulated and 49 downregulated genes. Pathway enrichment analysis of the DEGs examined the Ras signaling pathway, alcoholism, and other factors. Ultimately, eight prioritized genes (GNGT1, GNG4, NMU, GCG, TAC1, GAST, GCGR1, and NPSR1) were identified as hub genes. High hub gene expression was significantly associated with worse overall survival in patients with NSCLC. The ROC curves showed that these hub genes had diagnostic value. The mRNA expressions of GNGT1 and NMU were low in the Oncomine database. Their protein expressions and genetic alterations were also revealed. Finally, logistic regression analysis indicated that combining the two biomarkers substantially improved the ability to discriminate NSCLC. GNGT1 and NMU identified in the current study may empower further discovery of the molecular mechanisms underlying NSCLC's initiation and progression.
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http://dx.doi.org/10.1155/2021/6696198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806402PMC
January 2021

Power and promise of exosomes as clinical biomarkers and therapeutic vectors for liquid biopsy and cancer control.

Biochim Biophys Acta Rev Cancer 2021 01 25;1875(1):188497. Epub 2020 Dec 25.

Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address:

Exosomes, microvesicles derived from the nuclear endosome and plasma membrane, can be released into the extracellular environment to act as mediators between the cell membrane and cytoplasmic proteins, lipids, or RNA. Exosomes are considered effective carriers of intercellular signals in prokaryotes and eukaryotes, because of their ability to efficiently transfer proteins, lipids, and nucleic acids between cellular compartments. Since the 2007 discovery that exosomes carry bioactive substances, exosomes have been intensively researched. In various physiological and pathological processes, exosomes play important biological roles by specifically combining with receptor cells and transmitting information. Their stable biological characteristics, diversity of contents, non-invasiveness path for introducing signaling molecules, and ability for rapid detection make exosomes a promising clinical diagnostic marker for potentially many pathological conditions, including cancers. Exosomes are not only considered biomarkers and prognostic disease factors, but also have potential as gene carriers and drug delivery vectors, and have important clinical significance and application potential in the fields of cancer diagnosis, prognosis, and treatment.
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http://dx.doi.org/10.1016/j.bbcan.2020.188497DOI Listing
January 2021

L. Attenuates Denervated Skeletal Muscle Atrophy via PPARα/NF-κB Pathway.

Front Physiol 2020 3;11:580223. Epub 2020 Dec 3.

Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Treatment options for denervated skeletal muscle atrophy are limited, in part because the underlying molecular mechanisms are not well understood. Unlike previous transcriptomics studies conducted in rodent models of peripheral nerve injury, in the present study, we performed high-throughput sequencing with denervated atrophic biceps muscle and normal (non-denervated) sternocleidomastoid muscle samples obtained from four brachial plexus injury (BPI) patients. We also investigated whether L. (FCL.) extract can suppress denervated muscle atrophy in a mouse model, along with the mechanism of action. We identified 1471 genes that were differentially expressed between clinical specimens of atrophic and normal muscle, including 771 that were downregulated and 700 that were upregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the differentially expressed genes were mainly enriched in the GO terms "structural constituent of muscle," "Z disc," "M band," and "striated muscle contraction," as well as "Cell adhesion molecules," "Glycolysis/Gluconeogenesis," "Peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway," and "P53 signaling pathway." In experiments using mice, the reduction in wet weight and myofiber diameter in denervated muscle was improved by FCL. extract compared to saline administration, which was accompanied by downregulation of the proinflammatory cytokines interleukin (IL)-1β and IL-6. Moreover, although both denervated groups showed increased nuclear factor (NF)-κB activation and PPARα expression, the degree of NF-κB activation was lower while PPARα and inhibitor of NF-κB IκBα expression was higher in FCL. extract-treated mice. Thus, FCL. extract suppresses denervation-induced inflammation and attenuates muscle atrophy by enhancing PPARα expression and inhibiting NF-κB activation. These findings suggest that FCL. extract has therapeutic potential for preventing denervation-induced muscle atrophy caused by peripheral nerve injury or disease.
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http://dx.doi.org/10.3389/fphys.2020.580223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744683PMC
December 2020

Power and Promise of Next-Generation Sequencing in Liquid Biopsies and Cancer Control.

Cancer Control 2020 Jul-Aug;27(3):1073274820934805

Department of Radiology, 12485The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China.

Traditional methods of cancer treatment are usually based on the morphological and histological diagnosis of tumors, and they are not optimized according to the specific situation. Precision medicine adjusts the existing treatment regimen based on the patient's genomic information to make it most suitable for patients. Detection of genetic mutations in tumors is the basis of precise cancer medicine. Through the analysis of genetic mutations in patients with cancer, we can tailor the treatment plan for each patient with cancer to maximize the curative effect, minimize damage to healthy tissues, and optimize resources. In recent years, next-generation sequencing technology has developed rapidly and has become the core technology of precise targeted therapy and immunotherapy for cancer. From early cancer screening to treatment guidance for patients with advanced cancer, liquid biopsy is increasingly used in cancer management. This is as a result of the development of better noninvasive, repeatable, sensitive, and accurate tools used in early screening, diagnosis, evaluation, and monitoring of patients. Cell-free DNA, which is a new noninvasive molecular pathological detection method, often carries tumor-specific gene changes. It plays an important role in optimizing treatment and evaluating the efficacy of different treatment options in clinical trials, and it has broad clinical applications.
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http://dx.doi.org/10.1177/1073274820934805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791471PMC
March 2021

New Therapeutic Options for Advanced Hepatocellular Carcinoma.

Cancer Control 2020 Jul-Aug;27(3):1073274820945975

Cancer Institute, 377323Nantong Tumor Hospital, Nantong, China.

Hepatocellular carcinoma (HCC), one of the most common lethal diseases in the world, has a 5-year survival rate of only 7%. Hepatocellular carcinoma has no symptoms in the early stage but obvious symptoms in the late stage, leading to delayed diagnosis and reduced treatment efficacy. In recent years, as the scope of HCC research has increased in depth, the clinical development and application of molecular targeted drugs and immunotherapy drugs have brought new breakthroughs in HCC treatment. Targeted therapy drugs for HCC have high specificity, allowing them to selectively kill tumor cells and minimize damage to normal tissues. At present, these targeted drugs are mainly classified into 3 categories: small molecule targeted drugs, HCC antigen-specific targeted drugs, and immune checkpoint targeted drugs. This article reviews the latest research progress on the targeted drugs for HCC.
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http://dx.doi.org/10.1177/1073274820945975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791453PMC
March 2021

Targeting Long Non-coding RNA to Therapeutically Regulate Gene Expression in Cancer.

Mol Ther Nucleic Acids 2020 Sep 10;21:712-724. Epub 2020 Jul 10.

Department of Radiology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei 230012, China; Cancer Institute, Nantong Tumor Hospital, Nantong 226631, China; Central Laboratory for Medical Research, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. Electronic address:

Long-chain non-coding RNAs (lncRNAs) are RNA molecules with a length greater than 200 nt and no function of encoding proteins. lncRNAs play a precise regulatory function at different levels of transcription and post-transcription, and they interact with various regulatory factors to regulate gene expression, and then participate in cell growth, differentiation, apoptosis, and other life processes. In recent years, studies have shown that the abnormal expression of lncRNAs is closely related to the occurrence and development of tumors, which is expected to become an effective biomarker in tumor diagnosis. The sequencing analysis of mutations in the whole tumor genome suggests that mutations in non-coding regions may play an important role in the occurrence and development of tumors. Therefore, in-depth study of lncRNAs is helpful to clarify the molecular mechanism of tumor occurrence and development and to provide new targets for tumor diagnosis and treatment. This review introduces the molecular mechanism and clinical application prospect of lncRNAs affecting tumor development from the perspective of gene expression and regulation.
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http://dx.doi.org/10.1016/j.omtn.2020.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412722PMC
September 2020

Targeting Colorectal Cancer Stem Cells as an Effective Treatment for Colorectal Cancer.

Technol Cancer Res Treat 2020 Jan-Dec;19:1533033819892261

National Engineering Laboratory for Rice and By-Product Deep Processing, College of Food Science and Engineering, Central South University of Forestry and Technology, Changsha, China.

As one of the common cancers that threaten human life, the recurrence and metastasis of colorectal cancer seriously affect the prognosis of patients. Although new drugs and comprehensive treatments have been adopted, the current treatment effect on this tumor, especially in advanced colorectal cancer, is still not satisfactory. More and more evidence shows that tumors are likely to be a stem cell disease. In recent years, the rise of cancer stem cell theory has provided a new way for cancer treatment. Studies have found that a small number of special cells in colorectal cancer tissues that induce tumorigenesis, proliferation, and promote tumor migration and metastasis, namely, colorectal cancer stem cells. Colorectal cancer stem cells are defined with a group of cell-surface markers, such as CD44, CD133, CD24, epithelial cell adhesion factor molecule, LGR5, and acetaldehyde dehydrogenase. They are highly tumorigenic, aggressive, and chemoresistant and thus are critical in the metastasis and recurrence of colorectal cancer. Therefore, targeting colorectal cancer stem cells may become an important research direction for the future cure of colorectal cancer.
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http://dx.doi.org/10.1177/1533033819892261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785997PMC
August 2020
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