MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer

Technol Cancer Res Treat. 2021 Jan-Dec:20:15330338211041191. doi: 10.1177/15330338211041191.

Abstract

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1.

Keywords: UHRF1; apoptosis; lung cancer; miR-9 to 1; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Apoptosis / genetics*
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Computational Biology
  • Disease Models, Animal
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Heterografts
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics
  • Male
  • Mice
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA Interference*
  • Transcriptome
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • CCAAT-Enhancer-Binding Proteins
  • MIRN92 microRNA, human
  • MicroRNAs
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases