miR-27b-5p targets RAB27A to regulate exosome secretion and migration of pancreatic cancer cells
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
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 PC. Although the role of exosomes in PC 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 PC. Methods By comparing the serum miRNA profiles of PC patients with those of healthy controls, the key inhibitory factor microRNA-27b-5p (miR-27b-5p) was identified. After verifying its direct targeting of RAB27A, overexpression of miR-27b-5p and RAB27A rescue experiments were conducted in PC cells. Combined with the detection of intracellular multivesicular bodies (MVBs), the mechanism by which this axis regulates exosome secretion and PC metastasis was explored. Results experiments demonstrated that miR-27b-5p, which plays a crucial regulatory role, was significantly downregulated in PC. Additionally, it significantly inhibited exosome secretion and migration ability of PC cells bothand. Through biological analysis and luciferase reporter experiments, it was confirmed that miR-27b-5p directly targets RAB27A. Notably, functional experiments in PC cells indicated that overexpression of miR-27b-5p inhibited the expres
Abstract
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 PC. Although the role of exosomes in PC 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 PC. Methods By comparing the serum miRNA profiles of PC patients with those of healthy controls, the key inhibitory factor microRNA-27b-5p (miR-27b-5p) was identified. After verifying its direct targeting of RAB27A, overexpression of miR-27b-5p and RAB27A rescue experiments were conducted in PC cells. Combined with the detection of intracellular multivesicular bodies (MVBs), the mechanism by which this axis regulates exosome secretion and PC metastasis was explored. Results experiments demonstrated that miR-27b-5p, which plays a crucial regulatory role, was significantly downregulated in PC. Additionally, it significantly inhibited exosome secretion and migration ability of PC cells bothand. Through biological analysis and luciferase reporter experiments, it was confirmed that miR-27b-5p directly targets RAB27A. Notably, functional experiments in PC 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 PC exosome secretion. Conclusions This study reveals a novel molecular mechanism: miR-27b-5p directly targets RAB27A to suppress PC cell migration. This regulatory axis may contribute to exosome-related metastatic phenotypes of PC.