MicroRNA-486-3p Targets Chymotrypsin C to Regulate Pancreatic Cancer Progression and Immunosuppressive Factor Expression

Yong  Tao; Chengniu  Chu; Dongjun  Sun; Junfeng  Xiang; Bo  Wu; Cong  LI; Wei  Cui

doi:10.18502/ijaai.v23i6.17381

Yong Tao Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China
Chengniu Chu Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China
Dongjun Sun Department of Information, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China
Junfeng Xiang Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China
Bo Wu Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China
Cong LI Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China
Wei Cui Department of General Surgery, XuanCheng People's Hospital, Affiliated Xuancheng Hospital of Wannan Medical College, AnHui, China

DOI: https://doi.org/10.18502/ijaai.v23i6.17381

Keywords: Cell proliferation; Chymotrypsin C; Immunosuppressive factor; MicroRNA-486-3p; Pancreatic cancer

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a common digestive system tumor with high mortality rates and a poor prognosis. Reports suggest that microRNA (miR)-486-3p in PDAC can be used as a diagnostic biomarker. This research aimed to elucidate the mechanisms by which miR-486-3p regulates PDAC progression.

miR-486-3p and chymotrypsin C (CTRC) expression in PDAC were measured using quantitative real-time polymerase chain reaction. Changes in the biological properties of PDAC cells were assessed by Transwell assay, scratch-wound assay, cell counting kit (CCK)-8 assay, and plate cloning assay. The protein expression of immunosuppressive factors (vascular endothelial growth factor, interleukin-6, and transforming growth factor-β) in PDAC cells was detected by western blot. Additionally, a subcutaneous graft tumor model was constructed to explore the influence of silencing miR-486-3p on PDAC in vivo.

PDAC showed a pronounced increase in miR-486-3p expression. Upregulation of miR-486-3p stimulated PDAC cell proliferation, migration, invasion, and immunosuppressive factor protein expression, whereas silencing miR-486-3p hindered PDAC malignant development. miR-486-3p targets and negatively regulates CTRC expression. Silencing CTRC partially rescued the restraining impact of silencing miR-486-3p on PDAC malignant progression. In vivo experiments also indicated that silencing miR-486-3p inhibited PDAC malignant progression and immunosuppressive factor expression in vivo.

In summary, miR-486-3p promotes immunosuppressive factor protein expression by targeting and negatively regulating CTRC expression, which in turn promotes PDAC malignant progression.