title: Cisplatin regulates SH-SY5Y cell growth through downregulation of BDNF via miR-16.
abstract: Brain-derived neurotropic factor (BDNF) is a member of the neurotropin family. High levels of BDNF are associated with more aggressive malignant behavior in human cancer. In the present study, we observed the effect of cisplatin on BDNF expression in SH-SY5Y cells and investigated the mechanism of cisplatin in inducing the apoptosis of SH-SY5Y cells. Our results revealed that the expression of BDNF was obviously decreased in cisplatin-treated SH-SY5Y cells. In addition, the 3'-untranslated region of BDNF was found to be targeted by miR-16 using microRNA analysis software. After miR-16 was synthesized chemically, SH-SY5Y cells were transfected with miR-16 to investigate the regulatory role of miR-16 in regards to BDNF. The results showed that the expression of BDNF was markedly decreased in the miR‑16-transfected cells when compared with that in the control cultures as determined by western blotting. Moreover, miR-16 expression was obviously upregulated in the cisplatin-treated cells when compared with the untreated controls. Furthermore, SH-SY5Y cells were xenografted subcutaneously in nude mice to study the effect of cisplatin on the growth of SH-SY5Y cells in vivo. The results further showed that cisplatin inhibited the proliferation of SH-SY5Y cells in the cisplatin-treated mice when compared with the saline-treated control. The expression of miR-16 was increased, while the expression of BDNF was decreased in the cisplatin-treated mice. Our results demonstrated that cisplatin downregulated the expression of BDNF through miR-16 to inhibit SH-SY5Y cell proliferation in vitro and in vivo. These findings provide the basis for new targets for drug design or cancer therapy.
authors.affiliation: Department of Pediatrics, Qilu Hospital, Shandong University, Jinan 250012, P.R. China.
authors.forename: Yun-Xiao
authors.initials: YX
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.forename: Ping-Yu
authors.initials: PY
authors.lastname: Wang
authors.forename: You-Jie
authors.initials: YJ
authors.lastname: Li
authors.forename: Shu-Yang
authors.initials: SY
authors.lastname: Xie
authors.forename: Ruo-Peng
authors.initials: RP
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D019208:Brain-Derived Neurotrophic Factor; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; C579455:BDNF protein, human; D002945:Cisplatin