A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression

Sci Rep. 2018 Jan 17;8(1):900. doi: 10.1038/s41598-018-19259-4.

Abstract

We have previously demonstrated that Interleukin-27 differentially regulates the expression of seven novel microRNAs. Here we elucidate the functional significance of these novel microRNAs. Of the seven microRNAs, over expression of miRNA-6852 (miR-SX4) mimic induces cell cycle arrest at G2/M phase and induces necrosis in HEK293 and panel of cervical cancer cells (Human Papilloma Virus (HPV) infected cell lines; HeLa, CaSki and SiHa cells). To define the mechanism of the miR-SX4-mediated G2/M arrest, a microarray gene chip array and western blot analysis were performed. FoxM1, a transcription factor is identified as a key protein down-regulated by miR-SX4, even though the miR-SX4 does not target 3'UTR of FoxM1. Knock down of FoxM1 using si-RNA demonstrate that FoxM1 silenced cell induces G2/M cell cycle arrest and necrosis. Our data demonstrated for the first time that miR-SX4 could be a potent anti-cancer microRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Checkpoints / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics*
  • Female
  • Forkhead Box Protein M1 / genetics*
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Interleukins / genetics*
  • MicroRNAs / genetics*
  • Necrosis / genetics*
  • Uterine Cervical Neoplasms / genetics*

Substances

  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • IL27 protein, human
  • Interleukins
  • MicroRNAs