Hsa_circ_101280 promotes hepatocellular carcinoma by regulating miR-375/JAK2

Immunol Cell Biol. 2019 Feb;97(2):218-228. doi: 10.1111/imcb.12213. Epub 2018 Nov 26.

Abstract

In this study, we sought to predict the effects of a certain circular RNA (circRNA), hsa_circ_101280 (also known as hsa_circ_0100929 and hsa_circ_SLAIN1), on hepatocellular carcinoma (HCC) cells and to determine the potential mechanism. After screening differentially expressed circRNAs in HCC tissues through Gene Expression Omnibus data analysis, hsa_circ_101280 was found to be highly expressed, and its high expression was verified in HCC cell lines with qRT-PCR along with the low expression of its downstream miRNA miR-375. Colony formation and flow cytometry assays showed that both hsa_circ_101280 silencing and miR-375 overexpression restrained proliferation and promoted apoptosis in HCC cells. JAK2 was identified as a downstream mRNA target of miR-375 by RNA pull-down and dual-luciferase reporter gene assays, its expression in HCC cell lines were positively regulated by hsa_circ_101280 and negatively by miR-375 expression. Furthermore, the silencing of hsa_circ_101280 significantly inhibited the growth of HCC xenografts in nude mice, with the downregulated expression of JAK2. Overall, both the in vitro and in vivo studies revealed that hsa_circ_101280 largely facilitated the tumorigenesis of HCC, characterized by the promoted proliferation and suppressed apoptosis of HCC cells, by sponging miR-375 and upregulating JAK2.

Keywords: JAK2; Hepatocellular carcinoma; hsa_circ_101280; miR-375.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Janus Kinase 2 / metabolism*
  • Liver Neoplasms / genetics*
  • Mice, Nude
  • MicroRNAs / metabolism*
  • RNA, Circular / biosynthesis*
  • RNA, Circular / genetics
  • Transplantation, Heterologous

Substances

  • MIRN375 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Janus Kinase 2