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

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3 Scopus citations

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.

Original languageEnglish (US)
Article numbere0199827
JournalPloS one
Volume13
Issue number6
DOIs
StatePublished - Jun 2018
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Silakit, R., Kitirat, Y., Thongchot, S., Loilome, W., Techasen, A., Ungarreevittaya, P., Khuntikeo, N., Yongvanit, P., Yang, J. H., Kim, N. H., Yook, J. I., & Namwat, N. (2018). Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcitabine resistance in cholangiocarcinoma cells. PloS one, 13(6), [e0199827]. https://doi.org/10.1371/journal.pone.0199827