Elevated BTG2 improves the radiosensitivity of non-small cell lung cancer (NSCLC) through apoptosis

Thorac Cancer. 2022 May;13(10):1441-1448. doi: 10.1111/1759-7714.14410. Epub 2022 Apr 7.

Abstract

Background: To identify radio-responsive genes and explore the biological function of encoded proteins in non-small cell lung cancer (NSCLC).

Methods: Radio-responsive genes in irradiated H460 cells were screened from microarray data deposited in the Gene Expression Omnibus (GEO) database. A quantitative real time polymerase chain reaction assay was used to detect the expression of candidate radio-responsive genes in irradiated cells. CCK-8 assay, EDU assay, clone formation assay, immunofluorescence and flow cytometry were conducted to evaluate the biological function of B cell translocation gene 2 (BTG2) in NSCLC.

Results: Bioinformatic analysis using GES20549 showed that BTG2 was a radio-responsive gene in irradiated H460 cells. The mRNA expression level of BTG2 was lower in H460 cells compared with that in BEAS-2B normal lung epithelial cells. BTG2 expression was elevated upon IR exposure, in a dose-dependent but not a time-dependent manner. CCK-8 and EDU assays revealed that BTG2 overexpression inhibited the growth rate of irradiated cells. Clone formation showed that elevated BTG2 promoted DNA damage of irradiated H460 cells. The number of γ-H2AX foci induced by DNA damage was also markedly increased upon BTG2 overexpression. Flow cytometry showed that BTG2 increased IR-induced cell apoptosis.

Conclusions: BTG2 may be a novel radio-responsive factor and a promising therapeutic target for radiotherapy of NSCLC.

Keywords: BTG2; H460 cells; bioinformatics; biological function; radio-responsive genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / metabolism
  • Carcinoma, Non-Small-Cell Lung* / radiotherapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immediate-Early Proteins* / genetics
  • Immediate-Early Proteins* / metabolism
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / radiotherapy
  • Radiation Tolerance / genetics
  • Tumor Suppressor Proteins* / genetics
  • Tumor Suppressor Proteins* / metabolism

Substances

  • Immediate-Early Proteins
  • Tumor Suppressor Proteins
  • BTG2 protein, human