miR-22 enhances the radiosensitivity of small-cell lung cancer by targeting the WRNIP1

J Cell Biochem. 2019 Oct;120(10):17650-17661. doi: 10.1002/jcb.29032. Epub 2019 Jun 12.

Abstract

Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by high cellular proliferation and early distant metastasis. Our study aimed to explore the effect of miR-22-3p (miR-22, for short) on SCLC radiosensitivity and its molecular mechanisms. The expression level of miR-22 was evaluated in a human normal lung epithelial cell line and a human SCLC cell line, and cell apoptosis and migration were detected. The expression of the miR-22 direct target WRNIP1 mRNA and protein were explored. Five differentially expressed genes were detected. The miR-22 expression in NCI-H446 was significantly decreased, and miR-22 overexpression significantly promoted cell apoptosis. miR-22 overexpression could significantly inhibit the cell migration of SCLC cells, and miR-22 had a negative regulatory effect on WRNIP1 mRNA and protein levels. KLK8 was downregulated, and the messenger RNA (mRNA) of four other genes (PC, SCUBE1, STC1, and GPM6A) was upregulated mRNA in cells overexpressing miR-22, which was in accordance with the bioinformatics analysis. miR-22 could enhance the radiosensitivity of SCLC by targeting WRNIP1.

Keywords: DEGs; SCLC; WRNIP1; miR-22; radiosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism*
  • Apoptosis / genetics
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Radiation
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Radiation Tolerance / genetics*
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / pathology

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • MIRN22 microRNA, human
  • MicroRNAs
  • WRNIP1 protein, human
  • ATPases Associated with Diverse Cellular Activities