title: Linc00152 Functions as a Competing Endogenous RNA to Confer Oxaliplatin Resistance and Holds Prognostic Values in Colon Cancer.
abstract: Long noncoding RNAs act as crucial regulators in plenty of human cancers, yet their potential roles and molecular mechanisms in chemoresistance are poorly understood. This study showed that a novel lncRNA, long intergenic noncoding RNA 152 (Linc00152 ), promoted tumor progression and conferred resistance to oxaliplatin (L-OHP)-induced apoptosis in vitro and in vivo. It antagonized chemosensitivity through acting as a competing endogenous RNA to modulate the expression of miR-193a-3p, and then erb-b2 receptor tyrosine kinase 4 (ERBB4). Knockdown of ERBB4 in colon cancer cells decreased AKT phosphorylation, which resulted in decreased L-OHP resistance. Consistent with above findings, the specific AKT signaling inhibitor and activator were used, respectively, which demonstrated that Linc00152 contributed to L-OHP resistance at least partly through activating AKT pathway. Further studies indicated that Linc00152 was increased and appeared to be an independent prognostic factor for decreased survival and increased disease recurrence in stage II and III colon cancer patients undergoing L-OHP-based chemotherapy after surgery. Collectively, our findings established Linc00152 as a candidate prognostic indicator of outcome and drug responsiveness in colon cancer patients, and the involvement of competing endogenous RNAs mechanism in Linc00152/miR-193a-3p/ERBB4/AKT signaling axis may provide a novel choice in the investigation of drug resistance.
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Yue
authors.affiliation: Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Donglan
authors.initials: D
authors.lastname: Cai
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Changyi
authors.initials: C
authors.lastname: Fang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dongwang
authors.initials: D
authors.lastname: Yan
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D000077150:Oxaliplatin; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D009944:Organoplatinum Compounds; D062085:RNA, Long Noncoding; C000608524:long non-coding RNA Linc00152, human; D000077150:Oxaliplatin