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. 2022 Dec 31;23(1):378-392.
doi: 10.1080/15384047.2022.2041961.

Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer via the SCARA5-FAK axis

Yadong Han  1   2 , Xu Qian  1 , Teng Xu  1 , Yang Shi  1
Affiliations

Carcinoma-associated fibroblasts release microRNA-331-3p containing extracellular vesicles to exacerbate the development of pancreatic cancer via the SCARA5-FAK axis

Yadong Han et al. Cancer Biol Ther. .

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.

Keywords: Carcinoma-associated fibroblasts; FAK pathway; SCARA5; extracellular vesicles; miR-331-3p; pancreatic cancer.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
CAFs-derived EVs promote the proliferation, migration and invasion of PC cells.
Figure 2.
Figure 2.
SCARA5 is poorly expressed in PC.
Figure 3.
Figure 3.
miR-331-3p targets SCARA5 in PC cells.
Figure 4.
Figure 4.
CAFs-derived EVs transport miR-331-3p to inhibit the expression of SCARA5.
Figure 5.
Figure 5.
CAFs-derived EVs transport miR-331-3p to promote the proliferation, migration and invasion of PC cells.
Figure 6.
Figure 6.
CAFs-derived EVs transport miR-331-3p to promote the proliferation, migration and invasion of PC cells by suppressing SCARA5.
Figure 7.
Figure 7.
CAFs-derived EVs transport miR-331-3p to promote the tumorigenesis of PC in vivo.
Figure 8.
Figure 8.
Schematic diagram of the mechanism by which miR-331-3p delivered by CAFs-derived EVs affect PC.
See this image and copyright information in PMC

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