Knockdown of MUC1 by RNA Interference (siRNA) Influenced Vascular Endothelial Growth Factor Receptor (VEGFR2) and Suppression of Growth of Pancreatic Cancer Cells (PANC1)

Directorate of Education in Al-Najaf, Ministry of Education, Al-Najaf, Iraq

^* Corresponding author: altaher733@gmail.com

Abstract

MUC1 is overexpressed approximately in most of pancreatic adenocarcinomas and has been revealed to be linked with a worse prognosis, beside effectiveness, MUC1 hold for regulating cellular and developmental pathways. The objective of the current study is to downregulate the overexpression of MUC1 by small interfering RNA (siRNA) on PANC1 and to investigate its effect on vascular endothelial growth factor (VEGFR-2) expression. Besides MUC1, the expression levels of VEGFR2 were investigated in PANC1. Then the expression level of MUC1 was downregulated by using MUC1 specific siRNA approach to identify whether MUC1 is involved in the regulation of VEGFR-2 mRNA and protein, which were determined by QRT-PCR and Western blot, respectively. Interestingly, siRNA is considered an emerging approach in cancer cell therapy. Furthermore, the impact of MUC1 silencing in pancreatic adenocarcinoma cell lines was investigated. Transwell and Matrigel assays were performed to study the functional significance of MUC1 activity on cell migration and invasion, respectively. The present study indicates that targeting MUC1 by siRNA in pancreatic adenocarcinoma cells is associated with silencing of VEGFR-2 expression in both mRNA and protein levels, demonstrating that MUC1 regulates the main driver of angiogenesis and metastasis. The current study showed that targeting MUC1 with siRNA decreases pancreatic cancer cell proliferation, migration, and invasion, by significantly decreasing the expression of the potent angiogenic receptor VEGFR-2. Therefore, targeting MUC1 with siRNA can be exploited as a therapeutic option for pancreatic cancer treatment.