title: MicroRNA-302d downregulates TGFBR2 expression and promotes hepatocellular carcinoma growth and invasion.
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 distributionin vitro, and augmented tumorigenicityin 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.
authors.affiliation: Department of Critical Care Medicine, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Yue-Liang
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Critical Care Medicine, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Qiu-Ping
authors.initials: QP
authors.lastname: Xu
authors.affiliation: Department of Critical Care Medicine, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Guan
keywords: hepatocellular carcinoma; microRNA-302d; transforming growth factor beta type II receptor; tumor promoter; tumorigenicity