Inhibition of COA4 attenuates PDAC cell growth

 

Introduction:

Pancreatic ductal adenocarcinoma (PDAC), an aggressive malignancy with dismal patient prognosis, ranks seventh in cancer-related mortality. There is thus a necessity to reveal molecular mechanisms underlying the initiation and progression of PDAC in order to offer new insight of PDAC diagnosis and treatment. In previous genome-wide mRNA expression analyses of micro-dissected human pancreatic tissues, we detected a previously undocumented putative role of Cytochrome C Oxidase Assembly Factor 4 Homolog (COA4), which was markedly overexpressed in PDAC tissue compared to chronic pancreatitis (CP) and healthy tissue.

Aims:

To assess functional roles and potential molecular mechanisms of COA4 in PDAC.

Methods:

Transient transfection, RNAi, cell viability and proliferation assays, Western-Blot, flow cytometry.

Results:

COA4 is overexpressed in human PDAC tissues. Proliferative activity of PDAC cells was attenuated following COA4 knockdown using three independent siRNAs to transiently silencing COA4 expression in three different cell lines. Western blot results suggest that the growth control of COA4 is due to antiproliferative effects rather than increasing apoptosis. Moreover, the capacity for anchorage-independent growth was reduced in the absence of COA4 expression. Flow cytometry analyses indicated no significant alteration in each phase of cell cycle, with the exception of siRNA3 in S007 cell line, which produced a G2/M arrest.

Conclusion:

COA4 is known as a putative COX assembly factor and located in mitochondria. Knockdown of COA4 might therefore result in decreased protein metabolism, and mitochondrial protein import might be a relevant pathway to control PDAC cell growth. A potential utility of COA4 as a novel therapeutic target of PDAC will have to be assessed in further studies.