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Differential effects of WRAP53 transcript variants on non-small cell lung cancer cell behaviors
Yan Zhu1,2, Wenjie Sun1, Xueping Jiang1
1Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
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.
Insights
WD40-encoding RNA antisense to p53 (WRAP53) transcript variants differentially regulate non-small cell lung cancer cell behaviors. Their distinct functions depend on p53 expression status, impacting proliferation, cell cycle, and invasion.
Area of Science:
- Molecular Biology
- Cancer Research
- Gene Regulation
Background:
- The WD40-encoding RNA antisense to p53 (WRAP53) gene has three transcript variants involved in non-small cell lung cancer (NSCLC) progression.
- The precise mechanisms by which WRAP53 transcript variants influence NSCLC cell behaviors remain unclear.
Purpose of the Study:
- To elucidate the distinct roles of WRAP53 transcript variants in regulating NSCLC cell behaviors.
- To investigate the influence of p53 expression status on WRAP53-mediated effects in NSCLC cells.
Main Methods:
- Utilized siRNA to knockdown WRAP53-1α and WRAP53-1β in NSCLC cell lines (A549 with wild-type p53, H1975 with mutated p53).
- Assessed biological effects through colony formation, cell viability, apoptosis, cell cycle, migration, and invasion assays.
- Quantified p53 expression levels via immunoblotting.
Main Results:
- WRAP53-1α knockdown modulated p53 levels, suppressed proliferation and invasion in A549 cells, but promoted them in H1975 cells.
- WRAP53-1β knockdown promoted A549 cell growth and invasion without affecting p53 levels or H1975 cells.
- Combined knockdown of WRAP53-1α and WRAP53-1β induced apoptosis in A549 cells but not H1975 cells.
Conclusions:
- WRAP53 transcript variants exhibit distinct functions in NSCLC cells.
- The functional outcomes of WRAP53 variants are contingent upon the endogenous p53 expression status.
- WRAP53 variants represent potential therapeutic targets in NSCLC, with strategies needing to consider p53 status.
