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MicroRNA-1205 Suppresses Hepatocellular Carcinoma Cell Proliferation via a CSNK2B/CDK4 Axis.

ABSTRACT: Introduction: MicroRNAs (miRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) via modulating expression of their targeting mRNAs. The present study aimed to investigate the role of miR-1205 in HCC cell proliferation and investigate the underlying molecular mechanism. Methods: The effects of miR-1205 on proliferation ability of HCC cell lines were explored in vitro and in vivo. Real-time quantitative PCR (qPCR) analysis was performed to determine miR-1205 expression in HCC tissues and cell lines. Online prediction tools and luciferase assays were used to identify potential target genes of miR-1205. Western blot analysis and dual-luciferase assays were conducted to screen key signaling pathway proteins regulated by miR-1205 and its' target gene. Results: In vitro and in vivo experiments showed that miR-1205 inhibits the proliferation of HCC cells. Dual-luciferase assays showed that miR-1205 interacted with CSNK2B by directly targeting the miRNA-binding site in the CSNK2B sequence, and further qPCR analysis indicated that CSNK2B expression was increased in HCC tissues and negatively correlated with miR-1205 expression. Furthermore, CSNK2B significantly promoted HCC cell proliferation, and CSNK2B overexpression or knockdown attenuated the effects of miR-1205 overexpression or inhibition on HCC cell viability, respectively. Mechanistically, miR-1205 suppresses HCC cell proliferation via a CSNK2B/CDK4 axis. Conclusion: The present results indicated that miR-1205 suppressed HCC cell proliferation by directly targeting CSNK2B and thus inhibiting the CDK4/pRb cell cycle pathway.

SUBMITTER: Li X

PROVIDER: S-EPMC9834419 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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MicroRNA-1205 Suppresses Hepatocellular Carcinoma Cell Proliferation via a CSNK2B/CDK4 Axis.

Li Xiang X Xie Shujie S Xia Qin Q Yan Jia J Chen Shuhuai S Shen Jia J

Technology in cancer research & treatment 20230101

Introduction: MicroRNAs (miRNAs) play important roles in the progression of hepatocellular carcinoma (HCC) via modulating expression of their targeting mRNAs. The present study aimed to investigate the role of miR-1205 in HCC cell proliferation and investigate the underlying molecular mechanism. Methods: The effects of miR-1205 on proliferation ability of HCC cell lines were explored in vitro and in vivo. Real-time quantitative PCR (qPCR) analysis was performed to det ...[more]

PMID: 36617978

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Project description:PurposeHepatocellular carcinoma (HCC), a worldwide leading cause of morbidity and mortality, is the most frequent primary liver tumor. Most HCC patients are diagnosed with advanced liver cancer, resulting in a very low 5-year survival rate. Thus, there is an urgent need for the development of targeted therapies. In this study, we aimed to investigate the effect and mechanism of the miR-20a/EZH1 axis on the proliferation and metastasis of HCC and the inhibitory effect of the EZH1/EZH2 inhibitor UNC1999 on HCC.Materials and methodsThe expression of miR-20a in human HCC tissues and cell lines was detected using quantitative real-time PCR (qRT-PCR). The expressions of proteins were analyzed with immunohistochemistry and Western blotting. Luciferase assay was used to verify whether miR-20a targets EZH1 or EZH2. The effect of miR-20a on HCC progression was studied in vivo and in vitro. The tumor inhibitory effect of UNC1999 was confirmed in vivo. CCK8 assay, wound healing assay, cell migration and invasion assay were used to evaluate the synergistic effect of UNC1999 with sorafenib. RNA sequencing (RNA-seq) was performed to screen the differentially expressed genes in the Huh7 and SMMC7721 cell lines after UNC1999, sorafenib, and combination treatments.ResultsIn this study, miR-20a showed a lower expression in both HCC tissues and cell lines. MiR-20a inhibited the proliferation and migration of SMMC7721 and Huh7 cells. The results of the luciferase assay and Western blot analysis revealed that miR-20a directly targeted EZH1, a histone methyltransferase. We demonstrated that miR-20a negatively regulated the expression of EZH1 and inhibited the proliferation and metastasis of HCC by reducing H3K27 methylation. We found UNC1999 inhibited tumor cells proliferation and enhanced the inhibitory effect of sorafenib.ConclusionWe demonstrated that miR-20a suppresses the tumor proliferation and metastasis in HCC by directly targeting EZH1. UNC1999 can inhibit tumor proliferation in vivo and increase the sensitivity of hepatoma cell lines to sorafenib.

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MicroRNA-1205 Suppresses Hepatocellular Carcinoma Cell Proliferation via a CSNK2B/CDK4 Axis.

Publications

MicroRNA-1205 Suppresses Hepatocellular Carcinoma Cell Proliferation via a CSNK2B/CDK4 Axis.

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