Differential effects of WRAP53 transcript variants on non-small cell lung cancer cell behaviors

PLoS One. 2023 Jan 27;18(1):e0281132. doi: 10.1371/journal.pone.0281132. eCollection 2023.

Abstract

Background: The WD40-encoding RNA antisense to p53 (WRAP53) is an antisense gene of TP53 with three transcriptional start sites producing three transcript variants involved in the progression of non-small cell lung cancer. However, the mechanism by which these different transcript variants regulate non-small cell lung cancer cell behaviors is to be elucidated.

Methods: Two non-small cell lung cancer cell lines, A549 cells with wild-type p53 and H1975 with mutated p53, were transfected with WRAP53-1α and WRAP53-1β siRNA. The biological effects were assessed via colony formation, cell viability, apoptosis, cell cycle, wound healing and cell invasion assays, as well as immunoblotting.

Results: Knockdown of WRAP53-1α increased the mRNA and protein levels of p53; suppressed colony formation and proliferation of A549 cells but promoted them in H1975 cells; increased the proportion of cells in the G0/G1 phase in A549 cells but decreased that in H1975 cells; and suppressed migration and invasion in A549 cells but not in H1975 cells. Conversely, knockdown of WRAP53-1β had no effect on p53 expression; promoted the growth of A549 cells but not of H1975 cells; decreased the proportion of cells in the G0/G1 phase in A549 cells but not in H1975 cells; and promoted migration and invasion in A549 cells but not in H1975 cells. Knockdown of both WRAP53-1α and WRAP53-1β promoted apoptosis in A549 cells but not in H1975 cells.

Conclusions: WRAP53 transcript variants exerted different functions in non-small cell lung cancer cells and regulated non-small cell lung cancer cell behaviors depending on the p53 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Apoptosis / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Tumor Suppressor Protein p53
  • WRAP53 protein, human

Grants and funding

This study was supported by National Natural Science Foundation of China (81972852 and 81800429), Key Research & Development Project of Hubei Province (2020BCA069), Health Commission of Hubei Province Medical Leading Talent Project, Young and Middle-Aged Medical Backbone Talents of Wuhan (WHQG201902), Application Foundation Frontier Project of Wuhan (2020020601012221), and Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (ZNJC201922 and ZNJC202007). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.