TY - JOUR
T1 - Potential role of HIF-1-responsive microRNA210/HIF3 axis on gemcitabine resistance in cholangiocarcinoma cells
AU - Silakit, Runglawan
AU - Kitirat, Yingpinyapat
AU - Thongchot, Suyanee
AU - Loilome, Watcharin
AU - Techasen, Anchalee
AU - Ungarreevittaya, Piti
AU - Khuntikeo, Narong
AU - Yongvanit, Puangrat
AU - Yang, Ji Hye
AU - Kim, Nam Hee
AU - Yook, Jong In
AU - Namwat, Nisana
N1 - Publisher Copyright:
© 2018 Silakit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85049232203
UR - https://www.scopus.com/pages/publications/85049232203#tab=citedBy
U2 - 10.1371/journal.pone.0199827
DO - 10.1371/journal.pone.0199827
M3 - Article
C2 - 29953500
AN - SCOPUS:85049232203
SN - 1932-6203
VL - 13
JO - PloS one
JF - PloS one
IS - 6
M1 - e0199827
ER -