MicroRNA-125b inhibits tumorigenic properties of hepatocellular carcinoma cells through suppression of eukaryotic translation initiation factor 5A2 (elF5A2)

Hepatocellular carcinoma (HCC) is a primary liver malignancy and accounts for most of the total liver cancer cases. Lack of treatment options and late diagnosis contribute to high mortality rate of HCC. In eukaryotes, translation of messenger RNA (mRNA) to protein is a key process in protein biosynthesis in which initiation of translation involves interaction of different eukaryotic translation initiation factors (eIFs), ribosome subunits and mRNAs. Eukaryotic translation initiation factor 5A (eIF5A) is one of the eIFs involved in translation initiation and eIF5A2, one of its isoforms, is upregulated in various cancers including HCC as a result of chromosomal instability, where it resides. In HCC, eIF5A2 expression is associated with adverse prognosis such as presence of tumor metastasis and venous infiltration. Based on eIF5A2 functional studies, suppressing eIF5A2 expression by short interfering RNA alleviates the tumorigenic properties of HCC cellsin vitrowhile ectopic expression of eIF5A2 enhances the aggressiveness of HCC cellsin vivoandin vitroby inducing epithelial-mesenchymal transition. In conclusion, eIF5A2 is a potential prognostic marker as well as a therapeutic target for HCC.

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Inhibition of miR-15a-5p Promotes the Chemoresistance to Pirarubicin in Hepatocellular Carcinoma via Targeting eIF4E

Computational and Mathematical Methods in Medicine ◽

10.1155/2021/6468405 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Ying Zhang ◽

Qingsong Tie ◽

Zhiwei Bao ◽

Zhi Shao ◽

Lan Zhang

Keyword(s):

Hepatocellular Carcinoma ◽

Translation Initiation ◽

Hepg2 Cells ◽

Carcinoma Cells ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Experimental Basis ◽

Eukaryotic Translation ◽

Eukaryotic Translation Initiation ◽

Direct Target

Chemoresistance has become a primary hurdle in the therapeutic outcome of hepatocellular carcinoma. Substantial evidences have demonstrated that microRNAs (miRNAs) are closely associated with the chemoresistance of hepatocellular carcinoma (HCC). Our investigation is aimed at testifying the influence of microRNA-15a-5p (miR-15a-5p)/eukaryotic translation initiation factor 4E (eIF4E) on hepatocellular carcinoma resistance to pirarubicin (THP). In our study, miR-15a-5p expression was increased in THP-treated HepG2 cells. Downregulation of miR-15a-5p blocked cell growth and elevated cell apoptosis of HepG2 cells treated with THP. Moreover, eIF4E was verified as a direct target of miR-15a-5p by binding its 3 ′ -UTR, which was confirmed by luciferase report experiment. Additionally, eIF4E was negatively associated with the miR-15a-5p expression in HepG2 cells. Mechanically, eIF4E was proven as a specific downstream of miR-15a-5p and mediated the effects of miR-15a-5p on cell viability and apoptosis of HepG2 cells treated with THP. These findings supported that miR-15a-5p facilitated THP resistance of hepatocellular carcinoma cells by modulating eIF4E, thus providing an experimental basis that miR-15a-5p might act as a novel diagnostic target in hepatocellular carcinoma resistance to THP.

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