Global targetome analysis reveals critical role of miR-29a in pancreatic stellate cell mediated regulation of PDAC tumor microenvironment

• DOI: 10.1186/s12885-020-07135-2
• Publication Date: 2020-07-13T12:06:02Z
• Authors: Shatovisha Dey; Sheng Liu; Tricia D. Factora; Solaema Taleb; Primavera Riverah...; Lata Udari; Xiaoling Zhong; Jun Wan; Janaiah Kota
• Keywords: Hepatic stellate cell; Oncomir

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive forms malignancies with a nearly equal incidence and mortality rates in patients. stellate cells (PSCs) are critical players PDAC microenvironment to promote aggressiveness pathogenesis disease. Dysregulation microRNAs (miRNAs) have been shown play significant role progression PDAC. Earlier, we observed PSC-specific downregulation miR-29a pancreas, however, mechanism action molecule PSCs still be elucidated. The current study aims clarify regulation identifies functionally important downstream targets that contribute tumorigenic activities during progression. Methods In this study, using RNAseq approach, performed transcriptome analysis paired overexpressing control human (hPSCs). Enrichment was identified differentially expressed genes (DEGs). dataset were identified, which utilized create network interactions. Western blots top candidate hPSCs transfected mimic or scramble control. Results 202 genes, included 19 downregulated direct targets. Translational repression eight key pro-tumorigenic -fibrotic namely IGF-1, COL5A3, CLDN1, E2F7, MYBL2, ITGA6 ADAMTS2 by PSCs. Using pathway analysis, find modulates effectors IGF-1-p53 signaling may hinder carcinogenesis. We further observe regulatory pathways associated ECM remodeling tumor-stromal crosstalk, such as INS/IGF-1, RAS/MAPK, laminin interactions collagen biosynthesis. Conclusions Together, our presents comprehensive understanding PSCs, essential PSC-mediated pathogenesis. findings suggest an anti-tumorigenic context PSC-cancer cell crosstalk advocates for potential targeted therapies.