title: Has‑miR‑125a and 125b are induced by treatment with cisplatin in nasopharyngeal carcinoma and inhibit apoptosis in a p53‑dependent manner by targeting p53 mRNA.
abstract: MicroRNA (miRNA) is a class of non‑coding RNA, which targets mRNAs of interest and suppresses its expression by degradation or translational inhibition. miRNA (miR)‑125a and miR‑125b were previously demonstrated to translationally and transcriptionally inhibit the expression of p53. The observed downregulation of the protein level of p53 in cisplatin‑treated patients with nasopharyngeal carcinoma (NPC) indicates the association between cisplatin resistance, miR‑125a and miR‑125b. In the present study, through the detection of the expression levels of miR‑125a and miR‑125b, a significant upregulation of these miRs was demonstrated in cisplatin‑treated patients with NPC. As a consequence, the protein expression level of p53 decreased notably. To confirm the induction of miR‑125a and miR‑125b by treatment with cisplatin, a cisplatin‑resistant TW03 cell model (TW03/DDP) was constructed. As expected, in the TW03/DDP cells, the expression levels of miR‑125a and miR‑125b were upregulated, and this caused downregulation of p53. Ectopic expression of these miRNAs in the TW03 cell model sensitized TW03 to cisplatin by decreasing the protein expression levels of p53, whereas ectopic expression in the antisense oligos of these microRNAs demonstrated the opposite effect. In addition, the present demonstrated that the cisplatin‑induced expression of miR‑125a and miR‑125b inhibited cisplatin‑induced apoptosis in the TW03 cells by decreasing the protein expression levels of p53. Taken together, the present study revealed for the first time, to the best of our knowledge, that induction of the expression of miR‑125a and miR‑125b by treatment with cisplatin resulted in resistance to the cisplatin drug in the NPC cells.
authors.affiliation: Department of Medical, The First People's Hospital of Neijiang, Neijiang, Sichuan 641000, P.R. China.
authors.forename: Jian Jun
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Department of E.N.T, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Shi Xi
authors.initials: SX
authors.lastname: Liu
authors.affiliation: Department of E.N.T, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Mian Zhi
authors.initials: MZ
authors.lastname: Chen
authors.affiliation: Central Laboratory, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610000, P.R. China.
authors.forename: Zi Yi
authors.initials: ZY
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D009305:Nasopharynx / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin