miR-27b-5p targets RAB27A to regulate exosome secretion and migration of pancreatic cancer cells

Background: Exosomes are the key mediators of intercellular communication within the tumor microenvironment. Pancreatic cancer (PC) exhibits an abnormal increase in exosome secretion, and this abnormal secretion is closely associated with the invasive migration and metastatic progression of pancreatic cancer. Although the role of exosomes in pancreatic cancer metastasis has been confirmed, the precise molecular mechanism regulating this process remains unclear. This study aims to explore the regulatory mechanism of the exosome secretion cascade and its correlation with malignant migration in pancreatic cancer.

Methods: By comparing the serum miRNA profiles of pancreatic cancer patients with those of healthy controls, the key inhibitory factor miR-27b-5p was identified. After verifying its direct targeting of RAB27A, overexpression of miR-27b-5p and RAB27A rescue experiments were conducted in pancreatic cancer cells. Combined with the detection of intracellular multivesicular bodies (MVBs), the mechanism by which this axis regulates exosome secretion and pancreatic cancer metastasis was explored.

Results: In vitro experiments demonstrated that miR-27b-5p, which plays a crucial regulatory role, was significantly downregulated in pancreatic cancer. Additionally, it significantly inhibited exosome secretion and migration ability of pancreatic cancer cells both in vivo and in vitro. Through biological analysis and luciferase reporter experiments, it was confirmed that miR-27b-5p directly targets RAB27A. Notably, functional experiments in pancreatic cancer cells indicated that overexpression of miR-27b-5p inhibited the expression level of RAB27A, exosome secretion ability, and the metastatic potential of cancer cells. Finally, a RAB27A rescue experiment was conducted to verify that overexpression of RAB27A counteracted the inhibitory effect of miR-27b-5p overexpression on pancreatic cancer exosome secretion.

Conclusions: This study reveals a novel molecular mechanism: miR-27b-5p directly targets RAB27A to suppress pancreatic cancer cell migration. This regulatory axis may contribute to exosome-related metastatic phenotypes of pancreatic cancer.