- 期刊
- OpenAccess
Elevated PRP19 expression targets Bcl-2 and CASP3 expression to inhibit human lung adenocarcinoma cells apoptosis in vitro
摘要
Aims: The gene product of PRP19 besides constituting a central player in the spliceosomal machinery, functions in DNA damage repair, a process that aborts the hasty and unwarranted destruction of cell harbouring irreparable DNA damages by apoptosis. Such DNA alterations are common features underlying tumorigenesis. Based on our earlier report that PRP19 overexpression is inhibitory to proliferation in lung tumor cells, we further investigated the effect of elevated expression of PRP19 on cell survival. Methods: PRP19 expression was augmented in cultured A549 cells via plasmid transfection. Growing cells were subjected to various cell survival and apoptosis assays including CCK-8, DAPI, TUNEL and FITCAnnexin V staining. Lysates were obtained from harvested cells for immunoblotting for the assessment of expression of key apoptotic proteins. Results: Lung adenocarcinoma cells A549, overexpressing PRP19 via plasmid transfection exhibited delayed onset of apoptosis thereby prolonging their life span. Further test by western blot on key proteins involved in apoptosis regulation revealed that PRP19 overexpression led to augmented expression of anti-apoptotic Bcl-2 proteins while diminishing the expression of caspase-3. The expression of pro-apoptotic protein Bax, was unaltered among test and control groups. The Bcl-2 higher expression coupled with suppression of caspase-3 possibly underlies the in vitro inhibition of apoptosis following PRP19 upregulation. Conclusion: PRP19 overexpression resulted in a modest suppression of apoptosis to prevent the hasty destruction of cells with compromised genomic integrity. This is beneficial to the cell and may explain why PRP19 expression in tumor tissues is higher than in non-tumor tissues.