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

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.