RNA polymerase III subunit K is overexpressed and regulates cell proliferation in Pancreatic Ductal Adenocarcinoma

Introduction:

Pancreatic ductal adenocarcinoma (PDAC) which arises in exocrine glands of the pancreas is the seventh leading cause of global cancer deaths in industrialized countries. Late presentation and aggressive biology lead to poor prognosis. Therefore, it is imperative to reveal the underlying biology of PDAC. Our previous study provided a host of PDAC candidate target genes by processing large-scale expression profiling analyses. Among the results, RNA Polymerase III Subunit K (POLr3K), which is related to hypomyelinating leukodystrophy but previously not implicated in PDAC, was detected to be deregulated in PDAC.

Aims:

To identify the function role of POLr3K in PDAC progression.

Methods:

Gene knockdown via siRNA; cell proliferation and viability assays, RT-PCR, Western blot, Flow Cytometry/cell cycle analysis.

Results:

POLr3K is overexpressed in human PDAC tissues, as demonstrated at mRNA and Protein level. Significantly impaired cell viability and proliferation rate was observed in 3 different pancreatic cancer cell lines following siRNA-mediated knockdown of POLr3K. This effect was due to a decrease in proliferation, but not induction of cell apoptosis. Moreover, the capacity for anchorage-independent growth was distinctly reduced in the absence of POLr3K expression. However, cell cycle distribution analyse shows no obvious change in cell cycle progression.

Conclusion:

This study reveals that POLr3K is highly expressed in PDAC tissues and compared to chronic pancreatitis and healthy pancreas tissues and has a crucial role in growth regulation of PDAC. Therefore, POLr3K could be a potential target for PDAC clinical therapy and prognostic/predictive diagnostics.