Silence of lncRNA HEIH suppressed liver cancer cell growth and metastasis through miR-199a-3p/mTOR axis

J Cell Biochem. 2019 Oct;120(10):17757-17766. doi: 10.1002/jcb.29041. Epub 2019 May 29.

Abstract

Background/aims: High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines.

Methods: The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied.

Results: As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl-2, MMP-2, MMP-8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase-3. MicroRNA (miR)-199a-3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR-199a-3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR-199a-3p.

Conclusion: HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR-199a-3p, and thereby blockage of mTOR signaling.

Keywords: hepatocellular carcinoma; lncRNA HEIH; mTOR signaling; miR-199a-3p.

Publication types

  • Retracted Publication

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • mirn199 microRNA, human
  • TOR Serine-Threonine Kinases