MicroRNA-92a contributes to tumor growth of human hepatocellular carcinoma by targeting FBXW7.
Deregulation of microRNA-92a (miR-92a) has been reported in several human cancers and is associated with prognosis of patients. However, the clinical significance of miR-92a and the underlying mechanisms involved in hepatocarcinogenesis remain to be determined. The aim of the present study was to determine the role of miR-92a in hepatocellular carcinoma (HCC). The results showed that the expression of miR-92a was upregulated in HCC tissues as compared with matched tumor-adjacent tissues. A high expression of miR-92a was observed in HCC cell lines as compared with a non-transformed hepatic cell line. The gain- and loss-of-function studies revealed that miR-92a significantly promoted proliferation and cell cycle transition from G1 to S phase, and inhibited apoptosis of HCC cell in vitro. In tumor‑bearing nude mice, the downregulation of miR-92a suppressed tumor growth of HCC in vivo. miR-92a was inversely correlated with F-box and WD repeat domain-containing 7 (FBXW7) expression in HCC tissues. Furthermore, miR-92a negatively regulated FBXW7 abundance in HCC cells. In the present study, FBXW7 was identified as a direct target of miR-92a. Notably, alterations of FBXW7 expression abrogated the effects of miR-92a on HCC cell proliferation, cell cycle and apoptosis. Clinical association analysis revealed that a high expression of miR-92a was correlated with poor prognostic characteristics of HCC. Notably, the high expression of miR-92a conferred a reduced 5-year overall survival (OS) and recurrence-free survival (RFS) of HCC patients. The multivariate Cox regression analysis demonstrated that miR-92a expression was an independent prognostic marker for predicting survival of HCC patients. In conclusion, the results of the present study suggested that miR-92a promotes the tumor growth of HCC by targeting FBXW7 and may serve as a novel prognostic biomarker and therapeutic target for HCC.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Wei
W
Yang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Changwei
C
Dou
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Yufeng
Y
Wang
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Yuli
Y
Jia
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Chao
C
Li
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Xin
X
Zheng
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Kangsheng
K
Tu
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D044783:F-Box Proteins / Q000235:genetics*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D011379:Prognosis; D016019:Survival Analysis; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D015854:Up-Regulation
D018797:Cell Cycle Proteins; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D044767:Ubiquitin-Protein Ligases