miR-132 inhibits cell proliferation, invasion and migration of hepatocellular carcinoma by targeting PIK3R3

Abstract

MicroRNA-132 (miR‑132) has been reported to play a tumor suppressive role in different human malignancies. However, its role and underling mechanism in hepatocellular carcinoma (HCC) remains poorly defined due to lack of target gene information. In the present study, we demonstrated that the mean level of miR‑132 in hepatocellular carcinoma (HCC) tissues was significantly lower than that in matched tumor-adjacent tissues, and its expression negatively correlated with tumor differentiation (P<0.01), TNM stage (P<0.01) and lymph node metastasis (P<0.01). Similarly, the expression of miR‑132 was obviously reduced in HCC cell lines as compared with a normal hepatic cell line. Ectopic expression of miR‑132 inhibited cell proliferation, colony formation, migration and invasion, and induced apoptosis in HepG2 cells. In vivo studies showed that miR‑132 inhibited tumor growth of HCC and decreased tumor volume and weight. In addition, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) was identified as a direct target of miR‑132 by a luciferase reporter assay. Western blot and qRT-PCR analysis indicated that PIK3R3 was significantly downregulated by miR‑132 in HCC cells. miR‑132 expression inversely correlated with PIK3R3 mRNA expression in clinical HCC tissues. Investigations into possible mechanisms revealed that miR‑132 inactivated the AKT/mTOR signaling pathway, which may contribute to inhibition of proliferation, migration, and invasion of HCC. These findings suggested that miR‑132 may serve as a potential target in the treatment of human HCC.

Regulatory role of miR-211-5p in hepatocellular carcinoma metastasis by targeting ZEB2

“…Reports showed that ZEB2 could be regulated by miR-139-5p in HCC which inhibits EMT and metastasis [21], miR-338-3p in gastric cancer cells which inhibits EMT [22], miRNA-200a in HCC suppresses metastatic potential of side population cells [23], miR-132 in lung cancer suppresses the migration and invasion [24] and others [25,26]. In HCC, there are other miRNAs like miR-132 and miR-206 which could inhibit hepatocellular carcinoma cell proliferation, metastasis and promote apoptosis of hepatocellular carcinoma [27,28]. A recent report shows that miR-154 and miR-141 functions as potential tumor suppressors targeting ZEB2 in HCC [29,30].…”

A five‐miRNA expression signature predicts survival in hepatocellular carcinoma

“…Expression level of miR‐132 is negatively correlated with tumor differentiation, TNM stage, and lymph node metastasis in HCC patients. miR‐132 inhibits cell proliferation, invasion, and migration of HCC by targeting PIK3R3 .…”

MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth

“…MicroRNAs (miRNAs) are a class of small non-coding RNAs, which direct post-transcriptional gene silencing (PTGS) and play important regulatory roles in a vast range of cellular processes including cell differentiation, proliferation, apoptosis, and migration [1–3]. Aberrant expression of miRNAs may play an important role in tumorigenesis or cancer development through dysregulation of tumor-associated genes [4–9].…”