Abstract
BackgroundZinc finger RNA binding protein (ZFR) is involved in the regulation of growth and cancer development. However, little is known about ZFR function in pancreatic cancer.MethodsHerein, to investigate whether ZFR is involved in tumor growth, Oncomine microarray data was firstly used to evaluate ZFR gene expression in human pancreatic tumors. Then short hairpin RNA (shRNA) targeting ZFR was designed and delivered into PANC-1 pancreatic cancer cells to knock down ZFR expression. Cell viability, cell proliferation and cell cycle analysis after ZFR knockdown were determined by MTT, colony forming and FACS, respectively. In addition, cell migration and invasion were assessed using the Transwell system.ResultsThe expression of ZFR was significantly higher in pancreatic tumors than normal pancreas tissues by Oncomine database analysis. Knockdown of ZFR by shRNA-expressing lentivirus significantly decreased the viability and invasion ability of pancreatic cancer cells. Moreover, FACS analysis showed that knockdown of ZFR in PANC-1 cells caused a significant cell cycle arrest at G0/G1 phase. Furthermore, knockdown of ZFR decreased the levels of CDK2, CDK4, CyclinA and CyclinD1 and enhanced the expression of p27, which has evidenced by qRT-PCR and Western blot analysis.ConclusionsKnockdown of ZFR might provide a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.
Highlights
Zinc finger RNA binding protein (ZFR) is involved in the regulation of growth and cancer development
The human ZFR appears to be involved in the regulation of alternative pre-mRNA splicing [10] and was identified in a screen for factors that interact with the pre-mRNA splicing activator RNPS1 [11]
ZFR is upregulated in pancreatic cancer ZFR mRNA levels in human pancreatic cancer tissues were investigated using two datasets from the publicly available oncomine database
Summary
Zinc finger RNA binding protein (ZFR) is involved in the regulation of growth and cancer development. Little is known about ZFR function in pancreatic cancer. The five-year survival rate among patients with pancreatic cancer is less than 5 % [3, 4] and almost all the patients succumbed to their disease within 2 years [5]. Zinc finger proteins, encoded by zinc finger RNA binding (ZFR), has been reported to play an important role in DNA binding and regulate growth and development [7]. The murine ZFR protein was identified in a screen for RNAbinding proteins expressed during spermatogenesis [9]. The human ZFR appears to be involved in the regulation of alternative pre-mRNA splicing [10] and was identified in a screen for factors that interact with the pre-mRNA splicing activator RNPS1 [11]. Knockdown expression of ZFR through RNA interference in neurons relocated
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