RRC ID 69571
Author Ota Y, Takahashi K, Otake S, Tamaki Y, Okada M, Yan I, Aso K, Fujii S, Patel T, Haneda M.
Title Extracellular RNA transfer from non-malignant human cholangiocytes can promote cholangiocarcinoma growth.
Journal FEBS Open Bio
Abstract Extracellular vesicles (EV) within the cellular secretome are emerging as modulators of pathological processes involved in tumor growth through their ability to transfer donor-derived RNA into recipient cells. While the effects of tumor and stromal cell EVs within the tumor microenvironment have been studied, less is known about the contributions of normal, nontransformed cells. We examined the impact of EVs within the cellular secretome from nonmalignant cells on transformed cell growth and behavior in cholangiocarcinoma cells. These effects were enhanced in the presence of the pro-fibrogenic mediator TGF-β. We identified miR-195 as a TGF-β responsive miRNA in normal cells that can be transferred via EV to tumor cells and regulate cell growth, invasion, and migration. The effects of miR-195 involve modulation of the epithelial-mesenchymal transition through direct effects on the transcription factor Snail. These studies provide in vitro and in vivo evidence for the impact of normal cellular secretome on transformed cell growth, show the importance of EV RNA transfer, and identify mechanisms of EV-mediated transfer of miRNA as a contributor to tumor development, which may provide new therapeutic opportunities for targeting human cholangiocarcinoma.
Volume 11(12)
Pages 3276-3292
Published 2021-12-1
DOI 10.1002/2211-5463.13294
PMID 34510808
PMC PMC8634862
MeSH Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Cholangiocarcinoma / genetics* Cholangiocarcinoma / metabolism Cholangiocarcinoma / physiopathology Epithelial Cells / metabolism Epithelial-Mesenchymal Transition / genetics Extracellular Vesicles / genetics* Extracellular Vesicles / physiology Gene Expression Regulation / genetics Humans MicroRNAs / genetics* MicroRNAs / metabolism Neoplasm Invasiveness / genetics Secretome Signal Transduction / genetics Tumor Microenvironment / genetics
IF 2.231
Human and Animal Cells RBE(RCB1292) TFK-1(RCB2537)