RRC ID 72276
Author Kimura Y, Ohzawa H, Miyato H, Kaneko Y, Saito A, Takahashi K, Tojo M, Yamaguchi H, Kurashina K, Saito S, Hosoya Y, Lefor AK, Sata N, Kitayama J.
Title MiR-29b may suppresses peritoneal metastases through inhibition of the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells.
Journal Sci Rep
Abstract Peritoneal dissemination is a major metastatic pathway for gastrointestinal and ovarian malignancies. The miR-29b family is downregulated in peritoneal fluids in patients with peritoneal metastases (PM). We examined the effect of miR-29b on mesothelial cells (MC) which play critical a role in the development of PM through mesothelial-mesenchymal transition (MMT). Human peritoneal mesothelial cells (HPMCs) were isolated from surgically resected omental tissue and MMT induced by stimulation with 10 ng/ml TGF-β1. MiR-29b mimics and negative control miR were transfected by lipofection using RNAiMAX and the effects on the MMT evaluated in vitro. HPMC produced substantial amounts of miR-29b which was markedly inhibited by TGF-β1. TGF-β1 stimulation of HPMC induced morphological changes with decreased expression of E-cadherin and calretinin, and increased expression of vimentin and fibronectin. TGF-β1 also enhanced proliferation and migration of HPMC as well as adhesion of tumor cells in a fibronectin dependent manner. However, all events were strongly abrogated by simultaneous transfection of miR-29b. MiR-29b inhibits TGF-β1 induced MMT and replacement of miR-29b in the peritoneal cavity might be effective to prevent development of PM partly through the effects on MC.
Volume 12(1)
Pages 205
Published 2022-1-7
DOI 10.1038/s41598-021-04065-2
PII 10.1038/s41598-021-04065-2
PMID 34997082
PMC PMC8742040
MeSH Animals Antigens, CD / metabolism Cadherins / metabolism Calbindin 2 / metabolism Cell Adhesion Cell Line, Tumor Cell Movement Cell Proliferation Coculture Techniques Epithelial Cells / drug effects Epithelial Cells / metabolism* Epithelial Cells / pathology Epithelial-Mesenchymal Transition* / drug effects Fibronectins / metabolism Humans Mice, Inbred C57BL MicroRNAs / genetics MicroRNAs / metabolism Peritoneal Neoplasms / genetics Peritoneal Neoplasms / metabolism* Peritoneal Neoplasms / secondary Peritoneum / drug effects Peritoneum / metabolism* Peritoneum / pathology Transforming Growth Factor beta1 / pharmacology Vimentin / metabolism
IF 3.998
Human and Animal Cells NUGC-4(RCB1939) MKN45(RCB1001)