Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer via the SCARA5-FAK axis. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Han, Yadong; Qian, Xu; Xu, Teng; Shi, Yang
• Is Part Of: Cancer biology & therapy. Volume 23:Issue 1(2022)
• Page Start: 378
• Page End: 392
• Publication Date: 2022-12-31
• Subjects: Carcinoma-associated fibroblasts -- extracellular vesicles -- miR-331-3p -- SCARA5 -- pancreatic cancer -- FAK pathway; 616.99406
• DOI: 10.1080/15384047.2022.2041961
• Languages: English
• ISSNs: 1538-4047

Abstract

ABSTRACT: microRNA-331-3p (miR-331-3p) has been displayed as an oncogene in pancreatic cancer (PC). The current research set out to elucidate how miR-331-3p in carcinoma-associated fibroblasts (CAFs)-derived extracellular vesicles (EVs) facilitated the tumorigenesis in PC. First, a dual-luciferase reporter assay was adopted to investigate the relationship between miR-331-3p and SCARA5. In addition, EVs were isolated normal fibroblasts and CAFs, and these isolated EVs were co-cultured with PC cells. Cell proliferative and migrating/invasive potentials were further evaluated with the help of a CCK-8 and Transwell assays, respectively. Gain- and loss-of-function assays were also implemented to assess the role of miR-331-3p, SCARA5, and FAK pathway in PC cells. Lastly, xenograft nude mice were established to investigate the role of miR-331-3p in vivo . miR-331-3p negatively targeted SCARA5 and was highly expressed in CAFs-derived EVs, which accelerated the proliferative, migrating, and invasive potentials of PC cells. Meanwhile, over-expression of miR-331-3p enhanced the proliferative, migrating, and invasive properties of PC cells and promoted tumor growth in vivo by manipulating SCARA5/FAK axis, whereas SCARA5 countered the oncogenic effects of miR-331-3p. Overall, miR-331-3p in CAFs-derived EVs inhibits SCARA5 expression and activates the FAK pathway, thereby augmenting the progression of PC. Our study provides a potential therapeutic target for the treatment of PC.