title: MicroRNA-302a sensitizes testicular embryonal carcinoma cells to cisplatin-induced cell death.
abstract: Cisplatin is a commonly used chemotherapeutic agent for the treatment of several human malignancies, such as testicular germ cell tumors (TGCT). The toxic effects persist and those that are present long after chemotherapy affect the overall quality of life of patients. MicroRNAs (miRNAs) play important roles in the responses of cancer cells to chemotherapy and have been shown to modulate cell sensitivity to chemotherapeutic drugs. However, the relationship between miRNA expression and cisplatin sensitivity of TGCT has not been fully explored. In this study, the effects of miR-302a on cisplatin cytotoxicity in TGCT-derived cell line NTERA-2 (NT2) were evaluated. We found that expression levels of miR-302a were increased in cisplatin-treated NT2 cells. Up-regulation of miR-302a significantly increased the sensitivity of NT2 cells to cisplatin by enhancing cisplatin-induced G2/M phase arrest and the subsequent progression to apoptosis. MiR-302a also increased the killing effects of cisplatin by lowering the apoptotic threshold; the same result was also observed in another TGCT-derived cell line, NCCIT. Furthermore, miR-302a-enhanced cisplatin sensitivity was partially mediated through the down-regulation of p21 in NT2 cells. MiR-302a induced apoptosis was further enhanced by silencing of p53 in NT2 cells. p53 levels were inversely associated with the expression of Oct4, Sox2, and Nanog in response to cisplatin. Thus, targeting miR-302a may offer new therapeutic interventions in TGCT.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and Department of Cell and Developmental Biology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Lian
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Tian
authors.forename: Meng
authors.initials: M
authors.lastname: Liang
authors.forename: Mianmian
authors.initials: M
authors.lastname: Yin
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D018236:Carcinoma, Embryonal / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D018398:Homeodomain Proteins; C532169:MIRN302A microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin