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Although great progresses have been made in recent decades for treating many cancers with anticancer drugs, effective therapeutics methods for anti-GBC are still lacking. Therefore, investigations into identifying the mechanisms underlying the drug resistance of GBC are greatly needed. In this study, we show that miR-218-5p plays a critical role in gemcitabine resistance of GBC. miR-218-5p levels were significantly lower in GBC than adjacent non-cancer tissues, and which were also associated with patient prognosis. While miR-218-5p overexpression abrogated gemcitabine resistance of GBC cells, silencing of which exhibited the opposite effects. Via six microRNA targets prediction algorithms, we found that <jats:italic>PRKCE<\/jats:italic> is a potential target of miR-218-5p. Moreover, miR-218-5p overexpression repressed the luciferase activity of reporter constructs containing 3\u2032-UTR of <jats:italic>PRKCE<\/jats:italic> and also reduced <jats:italic>PRKCE<\/jats:italic> expression. Further studies revealed that miR-218-5p promotes sensitivity of gemcitabine by abolishing PRKCE-induced upregulation of <jats:italic>MDR1<\/jats:italic>\/P-gp. Taken together, our results imply that an intimate correlation between miR-218-5p and <jats:italic>PRKCE<\/jats:italic>\/<jats:italic>MDR1<\/jats:italic> axis abnormal expression is a key determinant of gemcitabine tolerance, and suggest a novel miR-218-5p-based clinical intervention target for GBC patients.<\/jats:p>","DOI":"10.1038\/cddis.2017.178","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T15:17:37Z","timestamp":1494515857000},"page":"e2770-e2770","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["miR-218-5p restores sensitivity to gemcitabine through PRKCE\/MDR1 axis in gallbladder cancer"],"prefix":"10.1038","volume":"8","author":[{"given":"Hui","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Wang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man-Mei","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Heng","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Mohan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,11]]},"reference":[{"key":"BFcddis2017178_CR1","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1002\/ijc.28161","volume":"133","author":"FA Castro","year":"2013","unstructured":"Castro FA, Koshiol J, Hsing AW, Devesa SS . 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