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

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.

scholarly journals Implications of the Use of Eukaryotic Translation Initiation Factor 5A (eIF5A) for Prognosis and Treatment of Hepatocellular Carcinoma

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Felix H. Shek ◽  
Sarwat Fatima ◽  
Nikki P. Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Translation Initiation ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation Initiation Factor ◽  
Eukaryotic Translation ◽  
Initiation Of Translation ◽  
Eukaryotic Translation Initiation ◽  
Hcc Cells

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.

scholarly journals miR-133a acts as a tumor suppressor in colorectal cancer by targeting eIF4A1

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769838 ◽  
Author(s):  
Wenfeng Li ◽  
Anqi Chen ◽  
Lingling Xiong ◽  
Ting Chen ◽  
Fengxing Tao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Translation Initiation ◽  
Colon Cancer Cell ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Eukaryotic Translation ◽  
Tumor Tissues ◽  
Colon Cancer Cell Lines ◽  
Eukaryotic Translation Initiation ◽  
Direct Target

Emerging evidence indicates that microRNAs play critical roles in carcinogenesis and cancer progression. In this study, miR-133a was found to be significantly downregulated in colon tumor tissues. We aimed to determine its biological function, molecular mechanisms, and direct target genes in colorectal cancer. From these results, we found that miR-133a was significantly downregulated in primary tumor tissues and colon cancer cell lines. Ectopic expression of miR-133a in colon cancer cell lines significantly suppressed cell growth, as evidenced by cell viability and colony formation assays, as well as reduced xenograft tumor growth in nude mice. However, the effect of miR-133a was abolished by the overexpression of eIF4A1. Moreover, miR-133a inhibited cellular migration and invasiveness. A luciferase activity assay revealed oncogene eukaryotic translation initiation factor 4A1 as a direct target gene of miR-133a, whose expression was inversely correlated with that of miR-133a. Our results demonstrate that miR-133a plays a pivotal role in colorectal cancer by inhibiting cell proliferation, invasion, and migration by targeting oncogenic eukaryotic translation initiation factor 4A1, which acts as a tumor suppressor and may provide a new potential therapeutic target in colorectal cancer.

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