Overlapping targets exist between the Par-4 and miR-200c axis which regulate EMT and proliferation of pancreatic cancer cells

作者：Archana Katoch, Vijay Lakshmi Jamwal, Mir Mohd Faheem, Sriram Kumar, Shantibhusan Senapati, Govind Yadav, Sumit G. Gandhi, Anindya Goswami · 发表于：Translational Oncology · 年份：2020 · DOI：10.1016/j.tranon.2020.100879 · 被引用次数：21 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Wnt/β-catenin signaling in development and cancer

The last decade has witnessed a substantial expansion in the field of microRNA (miRNA) biology, providing crucial insights into the role of miRNAs in disease pathology, predominantly in cancer progression and its metastatic spread. The discovery of tumor-suppressing miRNAs represents a potential approach for developing novel therapeutics. In this context, through miRNA microarray analysis, we examined the consequences of Prostate apoptosis response-4 (Par-4), a well-established tumor-suppressor, stimulation on expression of different miRNAs in Panc-1 cells. The results strikingly indicated elevated miR-200c levels in these cells upon Par-4 overexpression. Intriguingly, the Reverse Phase Protein Array (RPPA) analysis revealed differentially expressed proteins (DEPs), which overlap between miR200c- and Par-4-transfected cells, highlighting the cross-talks between these pathways. Notably, Phospho-p44/42 MAPK; Bim; Bcl-xL; Rb Phospho-Ser807, Ser811; Akt Phospho-Ser473; Smad1/5 Phospho-Ser463/Ser465 and Zyxin scored the most significant DEPs among the two data sets. Furthermore, the GFP-Par-4-transfected cells depicted an impeded expression of critical mesenchymal markers viz. TGF-β1, TGF-β2, ZEB-1, and Twist-1, concomitant with augmented miR-200c and E-cadherin levels. Strikingly, while Par-4 overexpression halted ZEB-1 at the transcriptional level; contrarily, silencing of endogenous Par-4 by siRNA robustly augmented the Epithelial-mesenchymal transition (EMT) markers, along wit...