miR-106b promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma

Yen, Chia-Sheng; Su, Zhi-Ru; Lee, Yi-Ping; Liu, I-Ting; Yen, Chia‐Jui

doi:10.3748/wjg.v22.i22.5183

Cited by 53 publications

(46 citation statements)

References 36 publications

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“…In our study, we found that CTC‐specific miR106b was positively related to the expression level of vimentin in CTCs. It has been reported that overexpression of miR‐106b was observed in a variety of human tumors, which plays an oncogenic role in tumor progression and prognosis, including colorectal cancer , gastric cancer , hepatocellular carcinoma , glioma tumors , renal cell carcinoma , and head and neck squamous cell carcinomas . MiR‐106b plays a functional role in promoting proliferation, migration, and invasion of cancer cells both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

et al. 2019

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Background The molecular phenotype of circulating tumor cells (CTCs) was associated with clinical outcome of patients with breast cancer. CTCs isolated from patients with metastatic breast cancer (MBC) display a unique microRNA (miRNA) expression profile. The aim of this study was to enhance the prognostic accuracy of the CTC phenotype in patients with MBC, by incorporating miRNA into a combined prediction model. Subjects, Materials, and Methods CTCs were detected by CellSearch and enriched by magnetic cell sorting. miRNA deep sequencing and quantitative polymerase chain reaction were used to screen and verify potentially CTC‐specific miRNA candidates. Patients with MBC were enrolled from two independent cohorts, and overall survival (OS) and chemotherapy response were analyzed. Results We screened and identified that miR‐106b was an upregulated molecule in patients with MBC with CTC ≥5/7.5 mL (n = 16) compared with patients with CTC = 0/7.5 mL (n = 16) and healthy donors (n = 8). The expression of CTC‐specific miR‐106b correlated with vimentin and E‐cadherin in CTC and acted as an independent factor for predicting OS (hazard ratio 2.157, 95% confidence interval [CI] 1.098–4.239, p = .026). Although CTC‐specific miR‐106b, E‐cadherin, and vimentin showed a prognostic potential independently, the prognostic performance for OS based on the combination of three markers was significantly enhanced in Cohort 1 (area under the curve [AUC] 0.752, 95% CI 0.658–0.847, n = 128) and further validated in Cohort 2 (AUC 0.726, 95% CI 0.595–0.856, n = 91). Besides, a combined model incorporating miR‐106b was associated with therapy response. Conclusion The phenotypic assemblies of CTC incorporating miR‐106b show enhanced prognostic accuracy of overall survival in patients with MBC. Implications for Practice In order to enhance the prognostic accuracy of the circulating tumor cell (CTC) phenotype in patients with metastatic breast cancer (MBC), this study screened and identified a CTC‐specific microRNA (miRNA), miR‐106b, as an upregulated molecule based on the comparison of miRNA profile between CTCs, primary tumors, and healthy blood donors. By incorporating miR‐106b into a combined prediction model, the prognostic accuracy of the CTC phenotype for patients with MBC was greatly improved in both the training and validation cohorts. This work provides clinical evidence supporting the prognostic potential of CTC‐specific miRNA for patients with MBC. These results indicate that developing CTC‐specific miRNAs as new biomarkers will help to further optimize personalized therapy.

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Section: Discussionmentioning

confidence: 99%

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

et al. 2019

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“…All six members of the miR-17 family (miR-17, 20a, 20b, 93, 106a, and 106b) have been shown to function as onco-miRs in multiple malignancies (12,13,(31)(32)(33)(34)(35)(36)(37). As they share the same seed sequence, they likely target common genes and function redundantly.…”

Section: Discussionmentioning

confidence: 99%

Lipid Nanoparticle–Mediated Delivery of Anti-miR-17 Family Oligonucleotide Suppresses Hepatocellular Carcinoma Growth

Huang

Magnus

Kaimal

et al. 2017

Molecular Cancer Therapeutics

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Hepatocellular carcinoma (HCC) is one of the most common human malignancies with poor prognosis and urgent unmet medical need. Aberrant expression of multiple members of the miR-17 family are frequently observed in HCC, and their overexpression promotes tumorigenic properties of HCC cells. However, whether pharmacologic inhibition of the miR-17 family inhibits HCC growth remains unknown. In this study, we validated that the miR-17 family was upregulated in a subset of HCC tumors and cell lines and its inhibition by a tough decoy inhibitor suppressed the growth of Hep3B and HepG2 cells, which overexpress the miR-17 family. Furthermore, inhibition of the miR-17 family led to a global derepression of direct targets of the family in all three HCC cell lines tested. Pathway analysis of the deregulated genes indicated that the genes associated with TGFβ signaling pathway were highly enriched in Hep3B and HepG2 cells. A miR-17 family target gene signature was established and used to identify RL01-17(5), a lipid nanoparticle encapsulating a potent anti-miR-17 family oligonucleotide. To address whether pharmacologic modulation of the miR-17 family can inhibit HCC growth, RL01-17(5) was systemically administrated to orthotopic Hep3B xenografts. Suppression of Hep3B tumor growth was observed and tumor growth inhibition correlated with induction of miR-17 family target genes. Together, this study provides proof-of-concept for targeting the miR-17 family in HCC therapy..

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“…Additionally, the consistent decline of miR-199a/b-3p in HCC and its significant correlation with poor prognosis of HCC patients has been elucidated, suggesting miR-199a/b-3p as a potential HBV therapeutic target. Gao et al Several studies have suggested the role of HBx protein in miRNA expression during HBV infection [67,96,98,106]. For example, the recent study, conducted on 120 patients with HBV-related HCC, has shown that the expression of miR-106b was significantly higher in HBV-related HCC patients in comparison to non-HBV/non-HCV-related HCC patients and suggested that HBx enhances miR-106b transcription and therefore promotes tumor progression in HBV-related HCC [98].…”

Section: Hbv Mirna Biomarkersmentioning

confidence: 99%

“…Gao et al Several studies have suggested the role of HBx protein in miRNA expression during HBV infection [67,96,98,106]. For example, the recent study, conducted on 120 patients with HBV-related HCC, has shown that the expression of miR-106b was significantly higher in HBV-related HCC patients in comparison to non-HBV/non-HCV-related HCC patients and suggested that HBx enhances miR-106b transcription and therefore promotes tumor progression in HBV-related HCC [98]. Transfection with the HBx expression plasmid has been recently used in an additional study by Yu et al [114] to investigate HBx-related regulation of miR-19a, miR-122, and miR-223 in malignant hepatocytes.…”

Section: Hbv Mirna Biomarkersmentioning

confidence: 99%

Importance of MicroRNAs in Hepatitis B and C Diagnostics and Treatment

Jelen¹,

Glavač²

2017

Advances in Treatment of Hepatitis C and B

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MicroRNAs (miRNAs) are small-sized RNAs with ability to regulate gene expression and have been recently discovered as promising diagnostic and therapeutic biomarkers in the field of clinical medicine and microbiology, specifically in viral diseases. Infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) often lead to chronic infections and development of liver hepatocellular carcinoma (HCC). Challenges in early diagnosis of HCC and rapid development of novel HCV antivirals call for identification of novel miRNA biomarkers. An extensive selection of single miRNAs and miRNA panels has been provided by accumulating studies, discovering miRNA potentials in HBV and HCV diagnostics and treatment. Currently, the diagnostic potential of miRNAs in HBV and HCV has not been established yet. However, a promising HCV treatment drug Miravirsen, a locked nucleic acid, complementary to miRNA-122, has entered a human clinical trial recently. In this review, we outline the role of miRNAs in HBV and HCV pathogenesis and differences in up-and downregulation of miRNAs upon HBV and HCV infection and HCC development.

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miR-106b promotes cancer progression in hepatitis B virus-associated hepatocellular carcinoma

Abstract: The data obtained in the present study suggests that HBx enhances miR-106b transcription to promote tumor progression in HBV-associated HCC.

Cited by 53 publications

References 36 publications

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

Incorporating MicroRNA into Molecular Phenotypes of Circulating Tumor Cells Enhances the Prognostic Accuracy for Patients with Metastatic Breast Cancer

Lipid Nanoparticle–Mediated Delivery of Anti-miR-17 Family Oligonucleotide Suppresses Hepatocellular Carcinoma Growth

Importance of MicroRNAs in Hepatitis B and C Diagnostics and Treatment

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