Long Intergenic Nonprotein Coding RNA 0152 Promotes Hepatocellular Carcinoma Progression by Regulating Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin Signaling Pathway through miR-139/PIK3CA

Am J Pathol. 2020 May;190(5):1095-1107. doi: 10.1016/j.ajpath.2019.11.010. Epub 2020 Jan 16.

Abstract

Hepatocellular carcinoma (HCC) ranks as the fifth most common cancer worldwide, and it is the primary histologic subtype of liver cancer, with high incidence and poor prognosis. Recently, numerous long noncoding RNAs have been reported to be associated with the tumorigenesis of HCC; however, the underlying mechanisms of long intergenic nonprotein coding RNA 0152 (LINC00152) action in HCC are poorly understood. Herein, we identified a significant up-regulation of LINC00152 in both HCC tissues and cell lines. Functional studies showed that knockdown of LINC00152 inhibited cell proliferation, migration, and invasion, but promoted cell apoptosis, indicating its oncogenic functions in HCC tumorigenesis. Mechanistically, LINC00152 functioned as an efficient miR-139 sponge, thereby releasing the suppression of PIK3CA (a target gene of miR-139). Anti-miR-139 rescued the inhibition of cell proliferation, migration, and invasion induced by LINC00152 knockdown. Similarly, PIK3CA-overexpressing plasmid also reversed miR-139-mediated biological functions in HCC cells. Taken together, our study revealed a crucial regulatory network of LINC00152/miR-139/PIK3CA axis in the tumorigenesis of HCC, implying that LINC00152 may be a biomarker and novel therapeutic target for further clinical therapy of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Carcinoma, Hepatocellular / pathology*
  • Class I Phosphatidylinositol 3-Kinases / metabolism*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Liver Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • MIRN139 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA Linc00152, human
  • MTOR protein, human
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases