Publications by authors named "Yibin Deng"

60 Publications

Formation of filamentous fungal pellets in aerobic granular sludge via reducing temperature and dissolved oxygen: Characteristics of filamentous fungi and denitrification performance.

Bioresour Technol 2021 Jul 26;332:125056. Epub 2021 Mar 26.

School of Civil Engineering, Southeast University, Nanjing 210096, China. Electronic address:

A lab-scale sequencing batch reactor (SBR) using glucose as carbon source was operated for 500 days to investigate the formation of filamentous organisms and their function on stability of AGS system. After 250 days' stable operation under conditions of 25 ± 2 °C and dissolved oxygen (DO) of 4-5 mg/L (stage I), the temperature and DO were reduced to 10 ± 2 °C and DO of 1-2 mg/L until 280 days (stage II), to induce the growth of filamentous microorganisms. After that until 500 days (stage III), overgrowth of filamentous microorganisms with relative abundances of up to 19.46%, formation of black filamentous fungal pellets, and reconstruction of AGS granules were observed in turn. The relation between settling of AGS (SVI 30-72 mL/g) and filamentous microorganisms was revealed. Filamentous pellets were purified and identified as fungal Bradymyces and Knufia, with stronger denitrification performance on nitrite than nitrate. The results indicated that filamentous fungal pellets contributed to good sludge settling performance and promoted the denitrification process in AGS.
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http://dx.doi.org/10.1016/j.biortech.2021.125056DOI Listing
July 2021

Biomineralized iron oxide-polydopamine hybrid nanodots for contrast-enhanced -weighted magnetic resonance imaging and photothermal tumor ablation.

J Mater Chem B 2021 02;9(7):1781-1786

Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.

Iron oxide nanoparticles (IO NPs) have become the focus of molecular imaging probes for contrast enhanced magnetic resonance (MR) imaging due to their intrinsic magnetic and biodegradable properties, as well as long blood half-lives and low toxicity. Massive efforts have been made to explore the IO NPs as T2-weighted MR contrast agents, which have high susceptibility to induce a long-range magnetic field that interferes with diagnosis. Thus, the development of IO NPs with potent T1 relaxivity might help in providing an alternative for clinically applied gadolinium chelates. Herein, biomineralized iron oxide-polydopamine hybrid nanodots (IO/PDA-NDs) have been constructed using albumin as the nanoreactors to induce nanoprecipitation and polymerization simultaneously, facilitating T1-weighted contrast-enhancement as well as photothermal therapeutic capability. The IO nanoclusters in IO/PDA-NDs have an r1 relaxivity of 5.79 mM-1 s-1 with a relatively low r2/r1 ratio of 1.71, demonstrating the preferable iron oxide based T1 contrast agents. The high photothermal conversion coefficient and tumor targeting effect of the hybrid nanodots could result in complete tumor ablation efficacy. The biomineralization method provides a promising approach for the integration of tumor diagnosis and treatment to achieve efficient cancer theranostics.
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http://dx.doi.org/10.1039/d1tb00032bDOI Listing
February 2021

Circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis.

Anticancer Drugs 2021 01;32(1):44-52

Department of Thyroid and Breast Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, China.

Circular RNAs (circRNAs) have been shown to play a functional role in a variety of cancers. However, few studies on circRNAs in estrogen receptor-positive breast cancer have been conducted. Here, we investigated the role of circRNA circTP63 in estrogen receptor-positive breast cancer progression and malignant behaviors. First, we observed increased expression of circTP63 in MCF7 cells relative to normal human mammary epithelial cell lines, such as DU4475 and MCF-10A, and the changed oncogenicity of MCF7 cells correlated with circTP63 overexpression and downregulation. Interestingly, a series of gain- and loss-of-function assays revealed that a higher level of FOXM1 was closely associated with MCF7 malignant behaviors induced by circTP63 overexpression. Further investigations showed that circTP63 sponged to miR-873-3p, which targeted FOXM1 mRNA and inhibited its expression. Mechanistically, circTP63 binds to miR-873-3p and prevents the targeting of FOXM1, thus inducing the progression and malignant behaviors of estrogen receptor-positive breast cancer, such as cell proliferation, cell cycle dysregulation, invasion, migration and even tumor growth. CircTP63 might be a potential biomarker or target to treat estrogen receptor-positive breast cancer patients in the future.
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http://dx.doi.org/10.1097/CAD.0000000000001010DOI Listing
January 2021

Serum protein-based nanoparticles for cancer diagnosis and treatment.

J Control Release 2021 Jan 19;329:997-1022. Epub 2020 Oct 19.

Jiangsu Key Laboratory of Neuropsychiatric Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China. Electronic address:

Serum protein as naturally essential biomacromolecules has recently emerged as a versatile carrier for diagnostic and therapeutic drug delivery for cancer nanomedicine with superior biocompatibility, improved pharmacokinetics and enhanced targeting capacity. A variety of serum proteins have been utilized for drug delivery, mainly including albumin, ferritin/apoferritin, transferrin, low-density lipoprotein, high-density lipoprotein and hemoglobin. As evidenced by the success of paclitaxel-bound albumin nanoparticles (Abraxane), serum protein-based nanoparticles have gained attractive attentions for precise biological design and potential clinical application. In this review, we summarize the general design strategies, targeting mechanisms and recent development of serum protein-based nanoparticles in the field of cancer nanomedicine. Moreover, we also concisely specify the current challenges to be addressed for a bright future of serum protein-based nanomedicines.
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http://dx.doi.org/10.1016/j.jconrel.2020.10.030DOI Listing
January 2021

Identifying and treating ROBO1 /DOCK1 prostate cancer: An aggressive cancer subtype prevalent in African American patients.

Prostate 2020 09 20;80(13):1045-1057. Epub 2020 Jul 20.

Department of Urology, University of Minnesota, Minneapolis, Minnesota.

Background: There is a need to develop novel therapies which could be beneficial to patients with prostate cancer (CaP) including those who are predisposed to poor outcome, such as African-Americans. This study investigates the role of ROBO1-pathway in predicting outcome and race-based disparity in patients with CaP.

Methods And Results: Aided by RNA sequencing-based DECIPHER-testing and immunohistochemical (IHC) analysis of tumors we show that ROBO1 is lost during the progressive stages of CaP, a prevalent feature in African-Americans. We show that the loss of ROBO1 predicts high-risk of recurrence, metastasis and poor outcome of androgen-deprivation therapy in radical prostatectomy-treated patients. These data identified an aggressive ROBO1 /DOCK1 sub-class of CaP. Combined genetic and IHC data showed that ROBO1 loss is accompanied by DOCK1/Rac1 elevation in grade-III/IV primary-tumors and Mets. We observed that the hypermethylation of ROBO1-promoter contributes to loss of expression that is highly prevalent in African-Americans. Because of limitations in restoring ROBO1 function, we asked if targeting the DOCK1 could be an ideal strategy to inhibit progression or treat ROBO1 metastatic-CaP. We tested the pharmacological efficacy of CPYPP, a selective inhibitor of DOCK1 under in vitro and in vivo conditions. Using ROBO1 and ROBO1 CaP models, we determined the median effective concentration of CPYPP for growth. DOCK1-inhibitor treatment significantly decreased the (a) Rac1-GTP/β-catenin activity, (b) transmigration of ROBO1 cells across endothelial lining, and (c) metastatic spread of ROBO1 cells through the vasculature of transgenic Zebrafish model.

Conclusion: We suggest that ROBO1 status forms as predictive biomarker of outcome in high-risk populations such as African-Americans and DOCK1-targeting therapy has a clinical potential for treating metastatic-CaP.
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http://dx.doi.org/10.1002/pros.24018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556361PMC
September 2020

Exosome-transmitted long non-coding RNA suppresses the progression of hepatocellular carcinoma.

Aging (Albany NY) 2020 06 27;12(12):11550-11567. Epub 2020 Jun 27.

Clinic Medicine Research Center of Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China.

Extracellular communication mediated by exosomes in a tumor microenvironment can substantially affect tumor progression. However, the effect of exosomal long non-coding RNA on hepatocellular carcinoma (HCC) is still unclear. In this study, expressions in patients with HCC and healthy controls were detected and compared. Results showed that was significantly reduced in HCC tissues and exosomes from the plasma of patients with HCC (<0.05) and was primarily encapsulated by exosomes. The patients with HCC and the healthy controls could be distinguished using exosomal (AUC=0.8028). The transfer of exosomal secreted by normal cells to HCC cells stimulated apoptosis and weakened the invasion and migration abilities of HCC cells to suppress their malignant biological behavior (<0.05). Additionally, exosomal was capable of inhibiting tumor growth in vivo and modulating the expression of by competitively binding to miR-9-5p. In conclusion, exosomal is a new favorable biomarker for clinically detecting HCC, and can be transmitted by exosomes from normal cells to HCC cells to inhibit the and development of HCC. Thus, exosomal is involved in the communication between normal cells and HCC cells during the onset of HCC.
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http://dx.doi.org/10.18632/aging.103302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343467PMC
June 2020

COVID-19: asymptomatic carrier transmission is an underestimated problem.

Epidemiol Infect 2020 06 11;148:e116. Epub 2020 Jun 11.

State Key Lab of Respiratory Disease, Institute for Public Health, School of Public Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R0), effective reproduction number (Rt) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R0, Rt and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.
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http://dx.doi.org/10.1017/S0950268820001235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322154PMC
June 2020

Visualization of two architectures in class-II CAP-dependent transcription activation.

PLoS Biol 2020 04 20;18(4):e3000706. Epub 2020 Apr 20.

Section of Transcription and Gene Regulation, The Hormel Institute, University of Minnesota, Austin, Minnesota, United States of America.

Transcription activation by cyclic AMP (cAMP) receptor protein (CAP) is the classic paradigm of transcription regulation in bacteria. CAP was suggested to activate transcription on class-II promoters via a recruitment and isomerization mechanism. However, whether and how it modifies RNA polymerase (RNAP) to initiate transcription remains unclear. Here, we report cryo-electron microscopy (cryo-EM) structures of an intact Escherichia coli class-II CAP-dependent transcription activation complex (CAP-TAC) with and without de novo RNA transcript. The structures reveal two distinct architectures of TAC and raise the possibility that CAP binding may induce substantial conformational changes in all the subunits of RNAP and transiently widen the main cleft of RNAP to facilitate DNA promoter entering and formation of the initiation open complex. These structural changes vanish during further RNA transcript synthesis. The observations in this study may reveal a possible on-pathway intermediate and suggest a possibility that CAP activates transcription by inducing intermediate state, in addition to the previously proposed stabilization mechanism.
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http://dx.doi.org/10.1371/journal.pbio.3000706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192510PMC
April 2020

A novel terpenoid class for prevention and treatment of KRAS-driven cancers: Comprehensive analysis using in situ, in vitro, and in vivo model systems.

Mol Carcinog 2020 08 15;59(8):886-896. Epub 2020 Apr 15.

Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.

Inhibiting the disease progression in KRAS-driven cancers after diagnosis has been a difficult task for clinicians to manage due to the lack of effective intervention/preventive therapies. KRAS-driven cancers depend on sustained KRAS signaling. Although developing inhibitors of KRAS signaling has proven difficult in the past, the quest for identifying newer agents has not stopped. Based on studies showing terpenoids as modulators of KRAS-regulated downstream molecular pathways, we asked if this chemical family has an affinity of inhibiting KRAS protein activity. Using crystal structure as a bait in silico, we identified 20 terpenoids for their KRAS protein-binding affinity. We next carried out biological validation of in silico data by employing in situ, in vitro, patient-derived explant ex vivo, and KPC transgenic mouse models. In this report, we provide a comprehensive analysis of a lup-20(29)-en-3b-ol (lupeol) as a KRAS inhibitor. Using nucleotide exchange, isothermal titration calorimetry, differential scanning fluorimetry, and immunoprecipitation assays, we show that lupeol has the potential to reduce the guanosine diphosphate/guanosine triphosphate exchange of KRAS protein including mutant KRAS . Lupeol treatment inhibited the KRAS activation in KRAS-activated cell models (NIH-panel, colorectal, lung, and pancreatic intraepithelial neoplasia) and patient tumor explants ex vivo. Lupeol reduced the three-dimensional growth of KRAS-activated cells. The pharmacokinetic analysis showed the bioavailability of lupeol after consumption via oral and intraperitoneal routes in animals. Tested under prevention settings, the lupeol consumption inhibited the development of pancreatic intraepithelial neoplasia in LSL-KRAS mice (pancreatic ductal adenocarcinoma progression model). These data suggest that the selected members of the triterpene family (such as lupeol) could be exploited as clinical agents for preventing the disease progression in KRAS-driven cancers which however warrants further investigation.
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http://dx.doi.org/10.1002/mc.23200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334075PMC
August 2020

A Case-Control Study of the Association Between the SPP1 Gene SNPs and the Susceptibility to Breast Cancer in Guangxi, China.

Front Oncol 2019 20;9:1415. Epub 2019 Dec 20.

Department of Medical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37-0.94, = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65-0.96, = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype ( = 0.007 and = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I-III compared with those with clinical stage IV ( = 0.012 and = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-A-T haplotype (OR = 0.69, 95% CI = 0.52-0.93, = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.
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http://dx.doi.org/10.3389/fonc.2019.01415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933604PMC
December 2019

Long non-coding RNA F11-AS1 inhibits HBV-related hepatocellular carcinoma progression by regulating NR1I3 via binding to microRNA-211-5p.

J Cell Mol Med 2020 01 27;24(2):1848-1865. Epub 2019 Dec 27.

Department of Infectious Diseases, The Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, China.

Long non-coding RNAs (lncRNAs) could regulate growth and metastasis of hepatocellular carcinoma (HCC). In this study, we aimed to investigate the mechanism of lncRNA F11-AS1 in hepatitis B virus (HBV)-related HCC. The relation of lncRNA F11-AS1 expression in HBV-related HCC tissues to prognosis was analysed in silico. Stably HBV-expressing HepG2.2.15 cells were established to explore the regulation of lncRNA F11-AS1 by HBx protein, as well as to study the effects of overexpressed lncRNA F11-AS1 on proliferation, migration, invasion and apoptosis in vitro. Subsequently, the underlying interactions and roles of lncRNA F11-AS1/miR-211-5p/NR1I3 axis in HBV-related HCC were investigated. Additionally, the influence of lncRNA F11-AS1 and miR-211-5p on tumour growth and metastasis capacity of HepG2.2.15 cells were studied on tumour-bearing nude mice. Poor expression of lncRNA F11-AS1 was correlated with poor prognosis in patients with HBV-related HCC, and its down-regulation was caused by the HBx protein. lncRNA F11-AS1 was proved to up-regulate the NR1I3 expression by binding to miR-211-5p. Overexpression of lncRNA F11-AS1 reduced the proliferation, migration and invasion, yet induced apoptosis of HepG2.2.15 cells in vitro, which could be abolished by overexpression of miR-211-5p. Additionally, either lncRNA F11-AS1 overexpression or miR-211-5p inhibition attenuated the tumour growth and metastasis capacity of HepG2.2.15 cells in vivo. Collectively, lncRNA F11-AS1 acted as a modulator of miR-211-5p to positively regulate the expression of NR1I3, and the lncRNA F11-AS1/miR-211-5p/NR1I3 axis participated in HBV-related HCC progression via interference with the cellular physiology of HCC.
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http://dx.doi.org/10.1111/jcmm.14881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991646PMC
January 2020

Genotypic Resistance Remains A Concern In Chronic Hepatitis B Patients With High Viral Load After Lamivudine And Adefovir Combination Therapy.

Pharmgenomics Pers Med 2019 21;12:297-303. Epub 2019 Oct 21.

Medical Examination Center, Affiliated Hospital of Youjiang Nationalities Medical College, Baise City, Guangxi Province, People's Republic of China.

Aims: Previous studies have shown that baseline high viral load is closely related to treatment response in chronic hepatitis B (CHB). This study was designed to evaluate the differences of treatment responses between de novo lamivudine (LAM) plus adefovir (ADV) combination therapy compared with entecavir monotherapy (ETV).

Methods: A total of 185 HBeAg-positive CHB patients with high viral load were enrolled and assigned to the LAM+ADV group (n=90) or ETV group (n=95). Clinical variables are extracted from medical records.

Results: No significant differences in baseline variables were found between the two groups before antiviral treatment. After 104 weeks of antiviral therapy, the mean HBV DNA viral load in the LAM+ADV group decreased from 8.01±0.65 log copies/mL to 0.41±1.04 log copies/mL, compared with 8.04±0.57 log copies/mL to 0.57±1.28 log copies/mL in the ETV group (P=0.35). The virological response rate of LAM+ADV group was 82.2% (74/90) at 104 weeks of treatment, and 80.0% (76/95) in the ETV group (P=0.70). For HBeAg serological responses, HBeAg loss occurred in 23.3% (21/90) and 17.9% (17/95) in the LAM+ADV group and the ETV group, respectively (P=0.36). HBeAg seroconversion was observed in 15.6% (14/90) and 15.8% (15/95) in the LAM+ADV group and ETV group, respectively (P=0.96). However, after 104 weeks of treatment, genotypic resistance was confirmed in 8 cases in the LAM+ADV group, a proportion of 8.8% (8/90), compared with an absence of genotypic resistance in the ETV group (P=0.003).

Conclusion: Both de novo combination therapy of LAM+ADV and ETV monotherapy could effectively inhibit HBV replication in patients with high viral load. However, the rate of genotypic resistance in LAM+ADV treatment remains a concern. For CHB patients with high viral load, ETV treatment may be superior.
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http://dx.doi.org/10.2147/PGPM.S224256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814354PMC
October 2019

Characterization of Novel Murine and Human PDAC Cell Models: Identifying the Role of Intestine Specific Homeobox Gene ISX in Hypoxia and Disease Progression.

Transl Oncol 2019 Aug 4;12(8):1056-1071. Epub 2019 Jun 4.

Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, MN. Electronic address:

Therapy failure and metastasis-associated mortality are stumbling blocks in the management of PDAC in patients. Failure of therapy is associated to intense hypoxic conditions of tumors. To develop effective therapies, a complete understanding of hypoxia-associated changes in genetic landscape of tumors during disease progression is needed. Because artificially immortalized cell lines do not rightly represent the disease progression, studying genetics of tumors in spontaneous models is warranted. In the current study, we generated a spectrum of spontaneous human (UM-PDC1; UM-PDC2) and murine (HI-PanL, HI-PancI, HI-PanM) models representing localized, invasive, and metastatic PDAC from a patient and transgenic mice (K-ras/Pdx/Ink4a/p16). These spontaneous models grow vigorously under hypoxia and exhibit activated K-ras signaling, progressive loss of PTEN, and tumorigenicity in vivo. Whereas UM-PDC1 form localized tumors, the UM-PDC2 metastasize to lungs in mice. In an order of progression, these models exhibit genomic instability marked by gross chromosomal rearrangements, centrosome-number variations, Aurora-kinase/H2AX colocalization, loss of primary cilia, and α-tubulin acetylation. The RNA sequencing of hypoxic models followed by qRT-PCR validation and gene-set enrichment identified Intestine-Specific Homeobox factor (ISX)-driven molecular pathway as an indicator PDAC aggressivness. TCGA-PAAD clinical data analysis showed high ISX expression correlation to poor survival of PDAC patients, particularly women. The functional studies showed ISX as a regulator of i) invasiveness and migratory potential and ii) VEGF, MMP2, and NFκB activation in PDAC cells. We suggest that ISX is a potential druggable target and newly developed spontaneous cell models are valuable tools for studying mechanism and testing therapies for PDAC.
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http://dx.doi.org/10.1016/j.tranon.2019.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556561PMC
August 2019

Inhibition of miR-148a-3p resists hepatocellular carcinoma progress of hepatitis C virus infection through suppressing c-Jun and MAPK pathway.

J Cell Mol Med 2019 02 18;23(2):1415-1426. Epub 2018 Dec 18.

Department of Infectious Diseases, The Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, China.

Objectives: The present study was committed to investigate the role of miR-148a-3p in HCC infected with hepatitis C virus (HCV) and the regulatory mechanism of miR-148a-3p/c-Jun/MAPK signalling pathway.

Methods: Differential analysis and GSEA analysis were performed with R packages. QRT-PCR and Western blot were used to detect RNA or protein level, respectively. The targeted relationship between miR-148a-3p and c-Jun was predicted by TargetScan database and determined by double luciferase reporter assay. MTT assay and flow cytometry were used to evaluate cell proliferation, cell cycle and cell apoptosis, respectively.

Results: C-Jun was up-regulated, and MAPK signalling pathway was activated in HCV-infected HCC cells. C-Jun expression regulated inflammation-related gene expression and had an influence on cell proliferation, cell cycle and cell apoptosis. MiR-148a-3p, down-regulated in HCV-infected HCC cells, could target c-Jun mRNA to suppress c-Jun protein expression.

Conclusions: MiR-148a-3p suppressed the proliferation of HCC cells infected with HCV through targeting c-Jun mRNA.
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http://dx.doi.org/10.1111/jcmm.14045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349179PMC
February 2019

DANCR contributed to hepatocellular carcinoma malignancy via sponging miR-216a-5p and modulating KLF12.

J Cell Physiol 2019 06 14;234(6):9408-9416. Epub 2018 Nov 14.

Clinic Medicine Research Center of Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical College for Nationalities, Guangxi Zhuang, China.

Long noncoding RNA (lncRNA) differentiation antagonizing nonprotein coding RNA (DANCR) has been identified as an oncogene in several cancers. However, the biological function and role of DANCR in hepatocellular carcinoma (HCC) remain unclear. Our current study aimed to investigate the detailed mechanism of DANCR in HCC. We found that DANCR was significantly upregulated in HCC cell lines in comparison to LO2 cells. Then, we observed that knockdown of DANCR could greatly inhibit Huh7 and HepG2 cell proliferation. In addition, HCC cell apoptosis was increased by silence of DANCR and meanwhile, cell cycle progression was blocked in G1 phase. Apart from these, downregulation of DANCR repressed HCC cell migration and invasion ability obviously. As predicted by the bioinformatics analysis, microRNA-216a-5p (miR-216a-5p) could serve as a direct target of DANCR. MiR-216a-5p has been reported to be involved in many cancers. Here, the correlation between miR-216a-5p and DANCR was confirmed using dual-luciferase reporter assay and radioimmunoprecipitation assay. Subsequently, Kruppel-like factor 12 (KLF12) exerts an important role in different tumor types. KLF12 can function as a downstream target of miR-216a-5p. Finally, the in vivo experiments were used and the data proved that DANCR also strongly suppressed HCC tumor growth in vivo via targeting miR-216a-5p and KLF12. In conclusion, our study indicated that DANCR might provide a new perspective for HCC treatment.
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http://dx.doi.org/10.1002/jcp.27625DOI Listing
June 2019

Four long noncoding RNAs as potential prognostic biomarkers for hepatocellular carcinoma.

J Cell Physiol 2019 06 11;234(6):8709-8716. Epub 2018 Nov 11.

Clinical Medicine Research Center of Hepatobiliary Diseases, Affiliated Hospital of Youjiang Medical College for Nationalities, Baise, China.

The study aimed to identify the long noncoding RNAs (lncRNAs) biomarkers for occurrence and prognosis of patients with hepatocellular carcinoma (HCC), and simultaneously to investigate the potential role of lncRNAs in the oncogenesis of HCC. The lncRNAs expression data and the corresponding clinical information of HCC samples were extracted from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes and lncRNAs were identified and the correlation networks were constructed. In this study, we identified 212 differentially expressed lncRNAs and 7,577 differentially expressed genes between liver HCC tumor tissues and normal tissue samples. And then, combining with clinical information, a total of 11 lncRNAs and 162 genes as HCC biomarkers were identified by comprehensive bioinformatics analysis. Further, through coexpress network analysis, we confirmed four lncRNAs (lncRNA_ANKRD10.IT1, lncRNA_CTD.2583A14.8, lncRNA_RP11.404P21.3, and lncRNA_RP11.488L18.10), which can serve as prognostic biomarkers for HCC. The four lncRNAs identified in this study may serve as a potential therapy target for HCC.
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http://dx.doi.org/10.1002/jcp.27530DOI Listing
June 2019

Heterozygous deletion of chromosome 17p renders prostate cancer vulnerable to inhibition of RNA polymerase II.

Nat Commun 2018 10 22;9(1):4394. Epub 2018 Oct 22.

Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.

Heterozygous deletion of chromosome 17p (17p) is one of the most frequent genomic events in human cancers. Beyond the tumor suppressor TP53, the POLR2A gene encoding the catalytic subunit of RNA polymerase II (RNAP2) is also included in a ~20-megabase deletion region of 17p in 63% of metastatic castration-resistant prostate cancer (CRPC). Using a focused CRISPR-Cas9 screen, we discovered that heterozygous loss of 17p confers a selective dependence of CRPC cells on the ubiquitin E3 ligase Ring-Box 1 (RBX1). RBX1 activates POLR2A by the K63-linked ubiquitination and thus elevates the RNAP2-mediated mRNA synthesis. Combined inhibition of RNAP2 and RBX1 profoundly suppress the growth of CRPC in a synergistic manner, which potentiates the therapeutic effectivity of the RNAP2 inhibitor, α-amanitin-based antibody drug conjugate (ADC). Given the limited therapeutic options for CRPC, our findings identify RBX1 as a potentially therapeutic target for treating human CRPC harboring heterozygous deletion of 17p.
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http://dx.doi.org/10.1038/s41467-018-06811-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197287PMC
October 2018

Drives Metastasis of Prostate Cancer in Caucasian and African-American Men and Is A Potential Therapeutic Target: Hypothesis Tested in Race-specific Models.

Clin Cancer Res 2018 12 7;24(24):6421-6432. Epub 2018 Aug 7.

Department of Urology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.

Purpose: Metastasis is the major cause of mortality in prostate cancer patients. Factors such as genetic makeup and race play critical role in the outcome of therapies. This study was conducted to investigate the relevance of in metastatic prostate cancer disease in Caucasian and African-Americans.

Experimental Design: We employed race-specific prostate cancer models, clinical specimens, clinical data mining, gene-microarray, transcription-reporter assay, chromatin-immunoprecipitation (ChIP), IHC, transgenic-(tgfl/fl) zebrafish, and mouse metastasis models.

Results: BMI1 expression was observed to be elevated in metastatic tumors (lymph nodes, lungs, bones, liver) of Caucasian and African-American prostate cancer patients. The comparative analysis of stage III/IV tumors showed an increased BMI1 expression in African-Americans than Caucasians. TCGA and NIH/GEO clinical data corroborated to our findings. We show that expression (i) positively correlates to metastatic () and (ii) negative correlates to tumor suppressor () levels in tumors. The correlation was prominent in African-American tumors. We show that BMI1 regulates the transcriptional activation of , and . We show the effect of pharmacological inhibition of BMI1 on the metastatic genome and invasiveness of tumor cells. Next, we show the anti-metastatic efficacy of BMI1-inhibitor in transgenic zebrafish and mouse metastasis models. Docetaxel as monotherapy has poor outcome on the growth of metastatic tumors. BMI1 inhibitor as an adjuvant improved the taxane therapy in race-based and models.

Conclusions: BMI1, a major driver of metastasis, represents a promising therapeutic target for treating advanced prostate cancer in patients (including those belonging to high-risk group).
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http://dx.doi.org/10.1158/1078-0432.CCR-18-1394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6295260PMC
December 2018

Vasodilator-stimulated phosphoprotein promotes liver metastasis of gastrointestinal cancer by activating a β1-integrin-FAK-YAP1/TAZ signaling pathway.

NPJ Precis Oncol 2018 23;2(1). Epub 2018 Jan 23.

1Tumor Microenvironment and Metastasis, The Hormel Institute, University of Minnesota, Austin, MN 55912 USA.

Extracellular matrix (ECM)-induced β1-integrin-FAK signaling promotes cell attachment, survival, and migration of cancer cells in a distant organ so as to enable cancer metastasis. However, mechanisms governing activation of the β1-integrin-FAK signaling remain incompletely understood. Here, we report that vasodilator-stimulated phosphoprotein (VASP), an actin binding protein, is required for ECM-mediated β1-integrin-FAK-YAP1/TAZ signaling in gastrointestinal (GI) cancer cells and their liver metastasis. In patient-derived samples, VASP is upregulated in 53 of 63 colorectal cancers and 43 of 53 pancreatic ductal adenocarcinomas and high VASP levels correlate with liver metastasis and reduced patient survival. In a Matrigel-based 3-dimensional (3D) culture model, short hairpin RNA (shRNA)-mediated VASP knockdown in colorectal cancer cells (KM12L4, HCT116, and HT29) and pancreatic cancer cells (L3.6 and MIA PaCa-1) suppresses the growth of 3D cancer spheroids. Mechanistic studies reveal that VASP knockdown suppresses FAK phosphorylation and YAP1/TAZ protein levels, but not Akt or Erk-related pathways and that YAP1/TAZ proteins are enhanced by the β1-integrin-FAK signaling. Additionally, VASP regulates the β1-integrin-FAK-YAP1/TAZ signaling by at least two mechanisms: (1) promoting ECM-mediated β1-integrin activation and (2) regulating YAP1/TAZ dephosphorylation at downstream of RhoA to enhance the stability of YAP1/TAZ proteins. In agreement with these, preclinical studies with two experimental liver metastasis mouse models demonstrate that VASP knockdown suppresses GI cancer liver metastasis, β1-integrin activation, and YAP1/TAZ levels of metastatic cancer cells. Together, our data support VASP as a treatment target for liver metastasis of colorectal and pancreatic cancers.
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http://dx.doi.org/10.1038/s41698-017-0045-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871906PMC
January 2018

Rational Design of Conjugated Photosensitizers with Controllable Photoconversion for Dually Cooperative Phototherapy.

Adv Mater 2018 Jun 3:e1801216. Epub 2018 Jun 3.

State Key Laboratory of Radiation Medicine and Protection, Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

High-performance photosensitizers are highly desired for achieving selective tumor photoablation in the field of precise cancer therapy. However, photosensitizers frequently suffer from limited tumor suppression or unavoidable tumor regrowth due to the presence of residual tumor cells surviving in phototherapy. A major challenge still remains in exploring an efficient approach to promote dramatic photoconversions of photosensitizers for maximizing the anticancer efficiency. Here, a rational design of boron dipyrromethene (BDP)-based conjugated photosensitizers (CPs) that can induce dually cooperative phototherapy upon light exposure is demonstrated. The conjugated coupling of BDP monomers into dimeric BDP (di-BDP) or trimeric BDP (tri-BDP) induces photoconversions from fluorescence to singlet-to-triplet or nonradiative transitions, together with distinctly redshifted absorption into the near-infrared region. In particular, tri-BDP within nanoparticles shows preferable conversions into both primary thermal effect and minor singlet oxygen upon near-infrared light exposure, dramatically achieving tumor photoablation without any regrowth through their cooperative anticancer efficiency caused by their dominant late apoptosis and moderate early apoptosis. This rational design of CPs can serve as a valuable paradigm for cooperative cancer phototherapy in precision medicine.
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http://dx.doi.org/10.1002/adma.201801216DOI Listing
June 2018

L3MBTL2 orchestrates ubiquitin signalling by dictating the sequential recruitment of RNF8 and RNF168 after DNA damage.

Nat Cell Biol 2018 04 26;20(4):455-464. Epub 2018 Mar 26.

Department of Oncology, Mayo Clinic, Rochester, MN, USA.

Cells respond to cytotoxic DNA double-strand breaks (DSBs) by recruiting DNA repair proteins to the damaged site. This recruitment is dependent on ubiquitylation of adjacent chromatin areas by E3 ubiquitin ligases such as RNF8 and RNF168, which are recruited sequentially to the DSBs. However, it is unclear what dictates the sequential order and recruits RNF168 to the DNA lesion. Here, we reveal that L3MBTL2 (lethal(3)malignant brain tumour-like protein 2) is the missing link between RNF8 and RNF168. We found that L3MBTL2 is recruited by MDC1 and subsequently ubiquitylated by RNF8. Ubiquitylated L3MBTL2, in turn, facilitates recruitment of RNF168 to the DNA lesion and promotes DNA DSB repair. These results identify L3MBTL2 as a key target of RNF8 following DNA damage and demonstrates how the DNA damage response pathway is orchestrated by ubiquitin signalling.
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http://dx.doi.org/10.1038/s41556-018-0071-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083879PMC
April 2018

CPTP: A sphingolipid transfer protein that regulates autophagy and inflammasome activation.

Autophagy 2018 21;14(5):862-879. Epub 2018 Feb 21.

a Hormel Institute , University of Minnesota , Austin, MN USA.

The macroautophagy/autophagy and inflammasome pathways are linked through their roles in innate immunity and chronic inflammatory disease. Ceramide-1-phosphate (C1P) is a bioactive sphingolipid that regulates pro-inflammatory eicosanoid production. Whether C1P also regulates autophagy and inflammasome assembly/activation is not known. Here we show that CPTP (a protein that traffics C1P from its site of phosphorylation in the trans-Golgi to target membranes) regulates both autophagy and inflammasome activation. In human epithelial cells, knockdown of CPTP (but not GLTP [glycolipid transfer protein]) or expression of C1P binding-site point mutants, stimulated an 8- to 10-fold increase in autophagosomes and altered endogenous LC3-II and SQSTM1/p62 protein expression levels. CPTP depletion-induced autophagy elevated early markers of autophagosome formation (Golgi-derived ATG9A-vesicles, WIPI1), required key phagophore assembly and elongation factors (ATG5, ATG7, ULK1), and suppressed MTOR phosphorylation and that of its downstream target, RPS6KB1/p70S6K. Wild-type CPTP overexpression exerted a protective effect against starvation-induced autophagy. In THP-1 macrophage-like surveillance cells, CPTP knockdown induced not only autophagy but also elevated CASP1/caspase-1 levels, and strongly increased IL1B/interleukin-1β and IL18 release via a NLRP3 (but not NLRC4) inflammasome-based mechanism, while only moderately increasing inflammatory (pyroptotic) cell death. Inflammasome assembly and activation stimulated by CPTP depletion were autophagy dependent. Elevation of intracellular C1P by exogenous C1P treatment (instead of CPTP inhibition) also induced autophagy and IL1B release. Our findings identify human CPTP as an endogenous regulator of early-stage autophagosome assembly and inflammasome-driven, pro-inflammatory cytokine generation and release.
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http://dx.doi.org/10.1080/15548627.2017.1393129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070007PMC
October 2019

Light-Responsive Nanoparticles for Highly Efficient Cytoplasmic Delivery of Anticancer Agents.

ACS Nano 2017 12 20;11(12):12134-12144. Epub 2017 Nov 20.

School of Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and School of Radiation Medicine and Protection, and ‡Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University , Suzhou 215123, China.

Stimuli-responsive nanostructures have shown great promise for intracellular delivery of anticancer compounds. A critical challenge remains in the exploration of stimuli-responsive nanoparticles for fast cytoplasmic delivery. Herein, near-infrared (NIR) light-responsive nanoparticles were rationally designed to generate highly efficient cytoplasmic delivery of anticancer agents for synergistic thermo-chemotherapy. The drug-loaded polymeric nanoparticles of selenium-inserted copolymer (I/D-Se-NPs) were rapidly dissociated in several minutes through reactive oxygen species (ROS)-mediated selenium oxidation upon NIR light exposure, and this irreversible dissociation of I/D-Se-NPs upon such a short irradiation promoted continuous drug release. Moreover, I/D-Se-NPs facilitated cytoplasmic drug translocation through ROS-triggered lysosomal disruption and thus resulted in highly preferable distribution to the nucleus even in 5 min postirradiation, which was further integrated with light-triggered hyperthermia for achieving synergistic tumor ablation without tumor regrowth.
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http://dx.doi.org/10.1021/acsnano.7b05214DOI Listing
December 2017

Bifunctional Tellurium Nanodots for Photo-Induced Synergistic Cancer Therapy.

ACS Nano 2017 10 2;11(10):10012-10024. Epub 2017 Oct 2.

School of Pharmacy, Air Force Military Medical University , Xi'an 710032, China.

Elemental tellurium (Te) nanoparticles are increasingly important in a variety of applications such as thermoelectricity, photoconductivity, and piezoelectricity. However, they have been explored with limited success in their biomedical use, and thus a tremendous challenge still exists in the exploration of Te nanoparticles that can treat tumors as an effective anticancer agent. Here, we introduce bifunctional Te nanodots with well-defined nanostructure as an effective anticancer agent for photo-induced synergistic cancer therapy with tumor ablation, which is accomplished using hollow albumin nanocages as a nanoreactor. Under near-infrared light irradiation, Te nanodots can produce effective photothermal conversion, as well as highly reactive oxygen species such as •O and dismutated •OH via a type-I mechanism through direct electron transfer, thereby triggering the potent in vivo hyperthermia and simultaneous intracellular reactive oxygen species at tumors. Moreover, Te nanodots possess perfect resistance to photobleaching, effective cytoplasmic translocation, preferable tumor accumulation, as well as in vivo renal elimination, promoting severe photo-induced cell damage and subsequent synergy between photothermal and photodynamic treatments for tumor ablation. These findings provide the insight of elemental Te nanodots for biomedical research.
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http://dx.doi.org/10.1021/acsnano.7b04230DOI Listing
October 2017

Ultrastable Near-Infrared Conjugated-Polymer Nanoparticles for Dually Photoactive Tumor Inhibition.

Adv Mater 2017 Aug 19;29(31). Epub 2017 Jun 19.

Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low-bandgap donor-acceptor (D-A)-type conjugated-polymer nanoparticles (CP-NPs) are developed to afford a highly efficient singlet-to-triplet transition and photothermal conversion for near-infrared (NIR) light-induced photodynamic (PDT)/photothermal (PTT) treatment. CP-NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP-NPs undergo singlet-to-triplet intersystem crossing through charge transfer in the excited D-A system and simultaneous nonradiative decay from the electron-deficient electron acceptor isoindigo derivative under single-wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP-NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light-triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP-NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof-of-concept design of D-A-type conjugated-polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.
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http://dx.doi.org/10.1002/adma.201700487DOI Listing
August 2017

Photoconversion-Tunable Fluorophore Vesicles for Wavelength-Dependent Photoinduced Cancer Therapy.

Adv Mater 2017 May 15;29(19). Epub 2017 Mar 15.

Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

Photoconversion tunability of fluorophore dye is of great interest in cancer nanomedicine such as fluorescence imaging, photodynamic therapy (PDT), and photothermal therapy (PTT). Herein, this paper reports wavelength-dependent photoconversional polymeric vesicles of boron dipyrromethene (Bodipy) fluorophore for either PDT under 660 nm irradiation or PTT under 785 nm irradiation. After being assembled within polymeric vesicles at a high drug loading, Bodipy molecules aggregate in the conformations of both J-type and H-type, thereby causing red-shifted absorption into near-infrared region, ultralow radiative transition, and ideal resistance to photobleaching. Such vesicles further possess enhanced blood circulation, preferable tumor accumulation, as well as superior cell uptake as compared to free Bodipy. In particular, the vesicles mainly generate abundant intracellular singlet oxygen for PDT treatment under 660 nm irradiation, while they primarily produce a potent hyperthermia for PTT with tumor ablation through singlet oxygen-synergized photothermal necrosis under 785 nm irradiation. This approach provides a facile and general strategy to tune photoconversion characteristics of fluorophore dyes for wavelength-dependent photoinduced cancer therapy.
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http://dx.doi.org/10.1002/adma.201606690DOI Listing
May 2017

Size-Dependent AgS Nanodots for Second Near-Infrared Fluorescence/Photoacoustics Imaging and Simultaneous Photothermal Therapy.

ACS Nano 2017 02 31;11(2):1848-1857. Epub 2017 Jan 31.

Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University , Suzhou 215123, China.

AgS nanoparticles are increasingly important in biomedicine, such as in cancer imaging. However, there has been only limited success in the exploration of theranostic AgS nanoparticles for photoinduced cancer imaging and simultaneous therapy. Here we report size-dependent AgS nanodots (NDs) with well-defined nanostructure as a theranostic agent for multimodal imaging and simultaneous photothermal therapy. The NDs are precisely synthesized through carefully controlled growth of AgS in hollow human serum albumin nanocages. These NDs produce effective fluorescence in second near-infrared (NIR-II) region, distinct photoacoustic intensity, and good photothermal conversion in a size-dependent manner under light irradiation, thereby generating sufficient in vivo fluorescence and photoacoustic signals as well as potent hyperthermia at tumors. Moreover, AgS NDs possess ideal resistance to photobleaching, effective cellular uptake, preferable tumor accumulation, and in vivo elimination, thus facilitating NIR-II fluorescence/photoacoustics imaging with both ultrasensitivity and microscopic spatial resolution and simultaneous photothermal tumor ablation. These findings provide insight into the clinical potential of AgS nanodots for cancer theranostics.
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http://dx.doi.org/10.1021/acsnano.6b07866DOI Listing
February 2017

Targeting IRES-Mediated p53 Synthesis for Cancer Diagnosis and Therapeutics.

Int J Mol Sci 2017 Jan 4;18(1). Epub 2017 Jan 4.

The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.

While translational regulation of p53 by the internal ribosome entry site (IRES) at its 5'-untranslated region following DNA damage has been widely accepted, the detailed mechanism underlying the translational control of p53 by its IRES sequence is still poorly understood. In this review, we will focus on the latest progress in identifying novel regulatory proteins of the p53 IRES and in uncovering the functional connection between defective IRES-mediated p53 translation and tumorigenesis. We will also discuss how these findings may lead to a better understanding of the process of oncogenesis and open up new avenues for cancer diagnosis and therapeutics.
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http://dx.doi.org/10.3390/ijms18010093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297727PMC
January 2017

Cyanine-Anchored Silica Nanochannels for Light-Driven Synergistic Thermo-Chemotherapy.

Small 2017 Feb 23;13(6). Epub 2016 Nov 23.

Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.

Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light-responsive nanoparticles that can maximize the potency of synergistic thermo-chemotherapy under light irradiation. Here, spatially confined cyanine-anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS-DOX-NCs) for light-driven synergistic cancer therapy are introduced. CS-DOX-NCs possess a J-type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π-π interaction with cyanine dye. Under near-infrared light irradiation, CS-DOX-NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J-type Cypate aggregates, trigger the light-driven drug release through the destabilization of temperature-sensitive π-π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species-mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS-DOX-NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light-driven nanoparticles for synergistic cancer therapy.
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http://dx.doi.org/10.1002/smll.201602747DOI Listing
February 2017