title: MicroRNA-137 chemosensitizes colon cancer cells to the chemotherapeutic drug oxaliplatin (OXA) by targeting YBX1.
abstract: The mechanisms underlying oxaliplatin (OXA) resistance in colon cancer cells are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. However, the relationship between miRNA and OXA resistance in colon cancer cells has not been previously explored. In this study, we utilized microRNA microarray analysis and real-time PCR to verify that miR-93, miR-191, miR-137, miR-181 and miR-491-3p were significantly down-regulated and that miR-96, miR-21, miR-22, miR-15b and miR-92 were up-regulated in both HCT-15/OXA and SW480/OXA cell lines. Blocking miR-137 caused a significant inhibition of OXA-induced cytotoxicity, therefore, miR-137 was chosen for further research. An in vitro cell viability assay showed that knockdown of miR-137 in HCT-15 and SW480 cells caused a marked inhibition of OXA-induced cytotoxicity. Moreover, we found that miR-137 was involved in repression of YBX1 expression through targeting its 3'-untranslated region. Furthermore, down-regulation of miR-137 conferred OXA resistance in parental cells, while over-expression of miR-137 sensitized resistant cells to OXA, which was partly rescued by YBX1 siRNA. The results of this study may aid the development of therapeutic strategies to overcome colon cancer cell resistance to OXA.
authors.affiliation: The First Hospital of Qinhuangdao, Hebei, China.
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Guo
authors.affiliation: The First Hospital of Qinhuangdao, Hebei, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pang
authors.affiliation: The Health Supervision Institude of Haigang District Qinhuangdao, Hebei, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Gao
authors.affiliation: The First Hospital of Qinhuangdao, Hebei, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: The First Hospital of Qinhuangdao, Hebei, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The First Hospital of Qinhuangdao, Hebei, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The First Hospital of Qinhuangdao, Hebei, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xuan
authors.affiliation: The First Hospital of Qinhuangdao, Hebei, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D051840:Y-Box-Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; D000077150:Oxaliplatin
keywords: Colon cancer; YBX1; drug resistance; miR-137