title: TUG1 mediates methotrexate resistance in colorectal cancer via miR-186/CPEB2 axis.
abstract: Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. Methotrexate (MTX) is one of the earliest cytotoxic drugs and serves as an anti-metabolite and anti-folate chemotherapy for various types of cancer. However, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the efficacy of MTX therapies in clinics. Long non-coding RNAs (lncRNAs) have gained widespread attention in recent years. More and more evidences have shown that lncRNAs play regulatory roles in various biological activities and disease progression including drug resistance in cancer cells. Here, we observed lncRNA TUG1 was associated to the MTX resistant in colorectal cancer cells. Firstly, quantitative analysis indicated that TUG1 was significantly increased in tumors which were resistant to MTX treatment. TUG1 knockdown re-sensitized the MTX resistance in colorectal cancer cells, which were MTX-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-186 could directly bind to TUG1, suggesting TUG1 might worked as a ceRNA to sponge miR-186. Extensively, our study also showed that CPEB2 was the direct target of miR-186 in colorectal cancer cells. Taken together, our study suggests that lncRNA TUG1 mediates MTX resistance in colorectal cancer via miR-186/CPEB2 axis.
authors.affiliation: Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China.
authors.forename: Changfeng
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, PR China. Electronic address: bile90566401130j@163.com.
authors.forename: Dayong
authors.initials: D
authors.lastname: Ding
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D019073:HT29 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; C554938:CPEB2 protein, human; C533096:MIRN186 microRNA, human; D035683:MicroRNAs; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; C000598536:TUG1 long noncoding RNA, human; D008156:Luciferases; D008727:Methotrexate
keywords: CPEB2; CRC; Colorectal cancer; Long noncoding RNA; MTX; Methotrexate; TUG1; miR-186