MicroRNA‐155‐5p promotes hepatocellular carcinoma progression by suppressing PTEN through the PI3K/Akt pathway

MicroRNA‐155‐5p (miR‐155‐5p) has been reported to play an oncogenic role in different human malignancies; however, its role in hepatocellular carcinoma (HCC) progression is not clearly understood. In this study, we used real‐time PCR in 20 rats with chemically‐induced HCC, 28 human HCC tissues, and the matched paracarcinoma tissues, and HCC cell lines to determine the expression patterns of miR‐155‐5p and PTEN mRNA. Algorithm‐based and experimental strategies, such as dual luciferase gene reporter assays, real‐time PCR and western blots were used to identify PTEN as a candidate miR‐155‐5p target. Gain‐ and loss‐of‐function experiments and administration of a PI3K/Akt pathway inhibitor (wortmannin) were used to identify the effects of miR‐155‐5p and PTEN in MTT assays, flow cytometric analysis, wound healing assays and transwell assays. The results showed that miR‐155‐5p was highly overexpressed; however, PTEN was underexpressed in the HCC rat models, human HCC tissues and cell lines. In addition, miR‐155‐5p upregulation and PTEN downregulation were significantly associated with TNM stage (P < 0.05). Through in vitro experiments, we found that miR‐155‐5p promoted proliferation, invasion and migration, but inhibited apoptosis in HCC by directly targeting the 3′‐UTR of PTEN. Western blots showed that miR‐155‐5p inactivated Bax and caspase‐9, but activated Bcl‐2 to inhibit apoptosis, and it activated MMP to promote migration and invasion via the PI3K/Akt pathway. A xenograft tumor model was used to demonstrate that miR‐155‐5p targets PTEN and activates the PI3K/Akt pathway in vivo as well. Our study highlighted the importance of miR‐155‐5p and PTEN associated with aggressive HCC both in vitro and in vivo.