MicroRNA-33a promotes cell proliferation and inhibits apoptosis by targeting PPARα in human hepatocellular carcinoma.

Weiping Chang,Zhaoxiang Yu,Lei Zhang,Yao Xian

doi:10.3892/etm.2017.4236

Abstract

MicroRNA-33a (miR-33a) is dysregulated in a number of human cancers, where it functions as an oncogenic miRNA. However, the clinical significance of miR-33a and its underlying molecular pathways regarding the progression of hepatocellular carcinoma (HCC) are currently unknown. In the present study, it was observed that the level of miR-33a expression was significantly increased in HCC tissues, relative to adjacent non-tumor tissues. Increased miR-33a expression was significantly correlated with poor prognostic features of HCC, including larger tumor size, higher Edmondson-Steiner grading and higher tumor-node-metastasis tumor stage. Furthermore, high levels of miR-33a expression were associated with decreases in the 5-year overall survival rate and recurrence-free survival of patients with HCC. In addition, functional experiments indicated that overexpression of miR-33a led to increased proliferation and reduced apoptosis of the HCC cell line Huh7, while knockdown of miR-33a decreased proliferation and induced apoptosis in the HCC cell line HepG2. Furthermore, peroxisome proliferator activated receptor alpha (PPARα) was identified as a direct target of miR-33a in HCC. Upregulation of miR-33a was found to reduce the levels of PPARα expression in Huh7 cells, while inhibition of miR-33a lead to a downregulation in PPARα expression in HepG2 cells. Collectively, these results suggest that miR-33a regulates the proliferation and apoptosis of HCC cells, and is a potential prognostic marker of HCC.

Highlights

IntroductionMicroRNAs (miRNAs) are an endogenous group of small (18‐25 nucleotides), non‐coding RNA molecules which serve
MicroRNAs are an endogenous group of small (18‐25 nucleotides), non‐coding RNA molecules which serveKey words: microRNA‐33a, hepatocellular carcinoma, proliferation, apoptosis, peroxisome proliferator activated receptor alpha key roles as post‐transcriptional regulators by binding to the 3'‐untranslated region (3'UTR) of target mRNA [1]
Increased miR‐33a expression in Hepatocellular carcinoma (HCC) correlates with adverse clinical features and poor prognosis

Summary

Introduction

MicroRNAs (miRNAs) are an endogenous group of small (18‐25 nucleotides), non‐coding RNA molecules which serve. Treatments for HCC have improved, the long‐term prognosis for patients with HCC remains poor, with a current 5‐year survival rate of ~30% [7,8]. A lack of biomarkers for early diagnosis and effective therapeutic targets are primary reasons for the poor disease outcomes. Studies into the molecular mechanisms of HCC pathogenesis are warranted, in order to identify potential biomarkers and therapeutic targets of HCC [9,10]. The roles of miRNAs in HCC have been investigated, with results indicating that the expression and/or function of miRNAs become aberrant in the pathogenesis of HCC [7]

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Results

Conclusion