MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion

Abstract

Abstract. Hepatocellular carcinoma (HCC) is the second leading cause of cancer-associated mortality in China and the third leading cause worldwide. A number of microRNAs (miRNAs) have been implicated in cell cycle progression, growth, apoptosis, angiogenesis and metastasis in HCC. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was used to detect the levels of miR-302d expression in the tissues of 30 patients with HCC. Cell cycle, growth, apoptosis and migration were analyzed using a cell counting kit, flow cytometry and a Transwell migration assay. Dual-luciferase reporter assays and western blotting were also used to analyze the expression levels of transforming growth factor beta type II receptor (TGFBR2) in HCC cells. The present study evaluated the role of miR-302d in the development and progression of HCC. Abnormally high expression of miR-302d was observed in 80% of HCC specimens. Moreover, patients with lower levels of miR-302d expression experienced a longer survival time than those with higher levels of miR-302d expression. It was demonstrated that miR-302d promoted HCC cell growth and migration, suppressed cell apoptosis and affected cell cycle distribution in vitro, and augmented tumorigenicity in vivo. Furthermore, TGFBR2, which is a tumor suppressor, was confirmed as a target of miR-302d in HCC cells. Dual-luciferase reporter assays indicated that TGFBR2 expression was negatively regulated by miR-302d. Taken together, the results of the present study suggest that miR-302d may serve as a valuable tool for predicting the prognosis of patients with HCC.

Role of microRNAs in the main molecular pathways of hepatocellular carcinoma

“…miR-302d: Chen and colleagues demonstrated that the overexpression of miR-302d promoted cell growth and migration and suppressed apoptosis in HCC cell lines and that it promotes xenograft tumor growth in vivo . These mechanisms were found to be mediated by TGFbR2-signaling, a target of miR-302d[ 37 ].…”

LncRNA GACAT1 Promotes Gastric Cancer Cell Growth, Invasion And Migration By Regulating MiR-149-mediated Of ZBTB2 And SP1

“…Non-coding RNAs have been strongly implicated in the development course of GC 10 , 11 , 12 . Noncoding RNAs include small ncRNAs (<200nt) and long ncRNAs(>200nt).…”

“…MicroRNAs, which are a class of small ncRNAs, have been widely investigated for their capacity to regulate genes through causing mRNA degradation or repressing protein translation 13 . Numerous microRNAs have been implicated as potential oncogenes or tumor suppressors affecting cancer development 11 , 14 , 15 . Relative to other noncoding RNAs, long ncRNAs (lncRNAs) lack evolutionary conservatism among species 16 , and thus the mechanisms of lncRNAs in human diseases are not fully understood.…”

Molecular signatures in hepatocellular carcinoma: A step toward rationally designed cancer therapy

“…Previous studies have causally linked individual microRNA expression changes to adverse biologic processes in HCC, including rapid proliferation, epithelial‐to‐mesenchymal transition (EMT), local tissue invasion, and vascular invasion . A summary of recently published studies with purported miRNA mechanisms is provided in Table . For the majority of cases, miRNA loss correlates to induction of a target oncogene, and miRNA gain correlates to repression of a target tumor suppressor.…”