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- Title
Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcitabine resistance in cholangiocarcinoma cells.
- Authors
Silakit, Runglawan; Kitirat, Yingpinyapat; Thongchot, Suyanee; Loilome, Watcharin; Techasen, Anchalee; Ungarreevittaya, Piti; Khuntikeo, Narong; Yongvanit, Puangrat; Yang, Ji Hye; Kim, Nam Hee; Yook, Jong In; Namwat, Nisana
- Abstract
MicroRNA-210 (miR-210) is a robust target for hypoxia-inducible factor, and its overexpression has been detected in a variety of solid tumors. However, the role of miR-210 in the development, progression and response to therapy in cholangiocarcinoma (CCA) remains undefined. We report here that high miR-210 expression was significantly correlated with the shorter survival of CCA patients. Overexpression of miR-210 inhibited CCA cell proliferation at the G2/M phase and reduced the gemcitabine sensitivity in CCA cells under CoCl2-induced pseudohypoxia. Concomitantly, inhibition of endogenous miR-210 activity using miRNA sponges increased cell proliferation under CoCl2-induced pseudohypoxia, resulting in an increase in gemcitabine sensitivity in CCA cells. We showed that HIF-3α, a negative controller of HIF-1α, was a target of miR-210 constituting a feed-forward hypoxic regulatory loop. Our data suggest an important role of miR-210 in sustaining HIF-1α activity via the suppression of HIF-3α, regulating cell growth and chemotherapeutic drug resistance in CCA.
- Subjects
MICRORNA; DISEASE progression; HYPOXEMIA; MACROPHAGES; CHOLANGIOCARCINOMA
- Publication
PLoS ONE, 2018, Vol 13, Issue 6, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0199827