CNOT3 contributes to cisplatin resistance in lung cancer through inhibiting RIPK3 expression

In this study, after screening theCNOT3 mRNA in a cancer microarray database called Oncomine and examining the expression levels ofCNOT3 mRNA in normal tissues and lung cancer tissues, we found thatCNOT3 was up-regulated in lung cancer tissues. Besides, its high-expression was associated with poor prognosis of lung cancer patients. We also found higher expression level of CNOT3 and lower expression level of receptor-interacting protein kinase 3 (RIPK3) in cisplatin-resistant A549 (A549/DDP) cells, and knocking down CNOT3 expression could sensitize A549/DDP cells to cisplatin-induced apoptosis. We demonstrated that CNOT3 depletion up-regulated the expression level of RIPK3 and the enhanced apoptosis was mediated by the elevated RIPK3 to further trigger Caspase 8 activation. Taken together, our results reveal a role of CNOT3 in cisplatin resistance of lung cancer and provide a potential target for lung cancer therapy.
Source: Apoptosis - Category: Molecular Biology Source Type: research