| RRC ID |
69571
|
| 著者 |
Ota Y, Takahashi K, Otake S, Tamaki Y, Okada M, Yan I, Aso K, Fujii S, Patel T, Haneda M.
|
| タイトル |
Extracellular RNA transfer from non-malignant human cholangiocytes can promote cholangiocarcinoma growth.
|
| ジャーナル |
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.
|
| 巻・号 |
11(12)
|
| ページ |
3276-3292
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
RBE(RCB1292)
TFK-1(RCB2537) |
