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.

Brain-Derived Neurotrophic Factor Mediated Perfluorooctane Sulfonate Induced-Neurotoxicity via Epigenetics Regulation in SK-N-SH Cells

“…Silio prediction and reporter system indicated that the level of BDNF, a central node in the miR-mRNA regulatory network, can be post-transcriptionally modulated by upregulated microRNA-30a-5p [31]. Yun reported that cisplatin can downregulate the expression of BDNF through increasing microRNA-16 to inhibit the proliferation of SH-SY5Y cells in vivo and vitro [32]. Our previous study indicated that PFOS most likely acted through microRNA-22 inhibiting the expression of BDNF in SH-SY5Y cells [11].…”

Use of Ferritin-Based Metal-Encapsulated Nanocarriers as Anticancer Agents

“…Furthermore, treatment of SH-SY5Y cells with free cisPt elicits slightly more cytotoxic effects than HFt-cisPt at higher concentrations (above 10 µM, Supplementary Figure S1), although other studies showed cytotoxicity of cisPt only at very high concentrations (e.g., Refs. [52,53]). …”

BDNF: An Oncogene or Tumor Suppressor?

“…cisplatin was also shown to increase production of microRNA-16 (miR-16) in neuroblastoma cells, which in turn reduced the levels of BDNF in a concentration-dependent manner (43). inhibition of BDNF production resulted in stunted neuroblastoma tumor growth in vivo (43) suggesting that, at least in part, BDNF's antagonism of cisplatin efficacy is due to the compensation of decreased BDNF levels mediated by cisplatin's activation of miR-16.…”

“…inhibition of BDNF production resulted in stunted neuroblastoma tumor growth in vivo (43) suggesting that, at least in part, BDNF's antagonism of cisplatin efficacy is due to the compensation of decreased BDNF levels mediated by cisplatin's activation of miR-16. other miRs that act antagonistic to BDNF production include MiR-206 in gastric cancer (44) and MiR-107 in non-small cell lung cancer (2).…”