miR-144 reverses cisplatin resistance in cervical cancer via targeting LHX2

J Cell Biochem. 2019 Sep;120(9):15018-15026. doi: 10.1002/jcb.28763. Epub 2019 Apr 24.

Abstract

Mounting evidence showed that microRNAs involve in development and chemoresistance of various human cancers. We explored the roles and mechanisms of miR-144 in resistance to cisplatin (CDDP) of cervical cancer cells. miR-144 and LIM homeobox 2 (LHX2) expression in CDDP-resistant and the parental cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis, respectively. The functions of miR-144 overexpression on cell viability, the incidence of apoptosis, the activity of caspase-3/7, the cleaved-caspase-3 expression, cell migration, and invasion were determined in Hela cells and Hela/CDDP cells. Overexpression of miR-144 reduced cell viability, induced cell apoptosis, and inhibited cell migration and invasion after CDDP treatment. Besides, a luciferase reporter system demonstrated that miR-144 could directly bind to the 3' untranslated region (3'-UTR) of LHX2 messenger RNA (mRNA). Gain expression of miR-144 decreased the expression of LHX2 both in mRNA and protein levels. Furthermore, restoration of LHX2 partly abolished the biological functions of miR-144 in resistance of cervical cancer cells. Taken together, miR-144 overcomes resistance to CDDP via promoting cell apoptosis and inhibiting invasion through targeting LHX2 in cervical cancer cells.

Keywords: cervical cancer; cisplatin; miR-144; resistance LXH2.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Survival / genetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • HeLa Cells
  • Humans
  • LIM-Homeodomain Proteins / genetics*
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • RNA, Messenger / genetics
  • Transcription Factors / genetics*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / genetics*

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • LHX2 protein, human
  • LIM-Homeodomain Proteins
  • MIRN144 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • Transcription Factors
  • Caspase 3
  • Caspase 7
  • Cisplatin