Extracellular vesicle-encapsulated miR-30e suppresses cholangiocarcinoma cell invasion and migration via inhibiting epithelial-mesenchymal transition

Abstract

Early-staged cholangiocarcinoma (CCA) is difficult to diagnose due to its high potential for invasion and metastasis. Epithelial-mesenchymal transition (EMT) is induced by transforming growth factor-β (TGF-β) in a process thought to be important for invasion and metastasis in several cancers, including CCA. Although microRNAs (miRNAs) have been implicated in the pathogenesis of several malignancies, their roles to CCA are not clearly understood. Some miRNAs were reported to be included in extracellular vesicles (EVs) and transferred from their donor cells to other cells, modulating recipient cell behaviors. In this study, the involvement and functional roles of EV-contained miRNAs during EMT in human CCA were determined. Expression profiling identified a subset of miRNAs that were reduced by TGF-β in CCA cells. Among these, miR-30e was highly downregulated by TGF-β and predicted to target Snail, which is an EMT-inducible transcription factor. MiR-30e overexpression suppressed cell invasion and migration via inhibiting EMT, whereas miR-30e inhibition promoted EMT, cell invasion and migration. Moreover, miR-30e was enriched in EVs derived from CCA cells after miR-30e overexpression, and miR-30e intercellular transfer through EVs suppressed EMT, cell invasion and migration in recipient CCA cells. Together, our results suggest that EV-mediated miR-30e transfer could inhibit EMT via directly targeting Snail, which subsequently suppresses CCA cell invasion and migration. These findings provide several new insights into regulatory mechanisms of tumor invasion and metastasis in human CCA.

The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer

“…This mechanism of EV-mediated intercellular communication has been revealed by several authors (13,(15)(16)(17). We previously reported that miR-30e could be transferred by cholangiocarcinoma (CCA) cell-derived EVs, and suppress recipient CCA cell invasion and migration (18). In PDAC, some investigators reported that EVencapsulated miRNAs, such as miR-196a, miR-1246, or miR-4644, could contribute to tumor development and play crucial roles in the diagnosis as tools of liquid biopsy (19)(20)(21).…”

“…We previously reported that EV-mediated transfer of lncRNAs or miRNAs can mediate the phenotypes of neighboring hepatocellular carcinoma (HCC), CCA, and PDAC cells (8,18,(24)(25)(26). Intercellular transfer of miR-30e by CCA cell-derived EVs could inhibit EMT signaling in recipient CCA cells (18). Also, long intergenic ncRNA regulator of reprogramming could be transferred by HCC cellderived EVs and suppress chemoresistance in recipient HCC cells (26).…”

Extracellular vesicles from senescent hepatic stellate cells promote cell viability of hepatoma cells through increasing EGF secretion from differentiated THP‑1 cells

“…Several studies have shown that the impact of EVs on surrounding cells varies by EV content and is regulated by cell conditions (41,42). Regarding the effect of EVs derived from senescent cells on cancer cells, Takasugi et al (43) showed that EVs derived from senescent cells are absorbed by several breast cancer cell lines via EphA2, which resulted in SASP factor-like cancer progression.…”

Nanoparticle mediated alteration of EMT dynamics: an approach to modulate cancer therapeutics

“…When miR-30e containing exosomes were used to treat CCA cells, there was suppression in cell invasion and migration, along with EMT inhibition. 143 TRIM59 gene is a tumour promoting factor in breast cancer cells, which modulates the PDCD10 and results in the suppression of its associated signalling pathway, ROCK 1. 144 miR-148b-3p is poorly expressed in breast cancer tissues as studied by Yuan., et al Human umbilical cord mesenchymal stem cell (HUCMSC) derived exosomes containing miR-148b-3p, when co-cultured with MDA MB-231 cell lines, induced downregulation of TRIM 59 gene expression, thereby suppressing the progression of breast cancer and inhibiting EMT.…”