Molecular medicine reports · 2015
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.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Chen Jian Jun, Liu Shi Xi, Chen Mian Zhi, Zhao Zi Yi
Аннотация
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.