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Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcitabine resistance in cholangiocarcinoma cells

 Runglawan Silakit  ;  Yingpinyapat Kitirat  ;  Suyanee Thongchot  ;  Watcharin Loilome  ;  Anchalee Techasen  ;  Piti Ungarreevittaya  ;  Narong Khuntikeo  ;  Puangrat Yongvanit  ;  Ji Hye Yang  ;  Nam Hee Kim  ;  Jong In Yook  ;  Nisana Namwat 
 PLoS One, Vol.13(6) : e0199827, 2018 
Journal Title
 PLoS One 
Issue Date
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-3alpha, a negative controller of HIF-1alpha, 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-1alpha activity via the suppression of HIF-3alpha, regulating cell growth and chemotherapeutic drug resistance in CCA.
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5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Yang, Ji Hye(양지혜)
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
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