Regulation of miR-142-3p on the sensitivity of neuroblastoma cells to CDDP by targeting HMGB1

Objectives: This study aims to investigate the influenceand underlying mechanism of miR-142-3p on the sensitivity of neuroblastoma cells to cis-diamine dichloroplatinum (CDDP). Methods: The CDDP-resistance neuroblastoma cell line SH-SY5Y/CDDP was constructed, and the expression level of miR-142-3p was detected by RTPCR. The apoptosis level and the IC50 value of SH-SY5Y/CDDP were quantified by CCK8 and Elisa. The 3'UTR of HMGB1 was cloned into the luciferase reporter vector to verify that miR-142-3p could target HMGB1. Results: The IC50 value of SH-SY5Y/CDDP increased from 4.57 +/- 0.65 mu g/mL to 23.53 +/- 3.87 mu g/mL, and it was 5.15 times higher than that of the parental cell line SH-SY5Y. The expression level of miR-142-3p in the SH-SY5Y/CDDP cells was remarkably lower than that in the SH-SY5Y cells. The differences were statistically significant (P<0.01). miR-1423p mimics significantly increased cell apoptosis, reduced HMGB1 expression and IC50 (7.02 +/- 1.38 vs 24.27 +/- 4.13 mu g/mL) to CDDPinSH-SY5Y/CDDP cells. In addition, miR-142-3p effectively inhibited the enzymatic activity of the luciferase driven by HMGB1 3'-UTR (P<0.01). In SH-SY5Y/CDDP cells after the knockdown of HMGB1 by siRNA, the apoptosis level was increased and the IC50 value of CDDP was significantly decreased. Conclusions: miR-142-3p can increase the sensitivity of neuroblastoma cells to CDDP by targeting HMGB1.