TUG1 knockdown 在顺铂耐药骨肉瘤中的抑癌作用通过抑制 MET/Akt 信号通路。

Anticancer potential of TUG1 knockdown in cisplatin-resistant osteosarcoma through inhibition of MET/Akt signalling.

机构信息

Department of Traditional Chinese Medicine, Ningbo Mingzhou Hospital, Ningbo, People's Republic of China.

Department of Orthopedics, Ningbo Fourth Hospital, Ningbo, People's Republic of China.

出版信息

J Drug Target. 2020 Feb;28(2):204-211. doi: 10.1080/1061186X.2019.1644651. Epub 2019 Jul 24.

DOI:10.1080/1061186X.2019.1644651

PMID:31305159

Abstract

Development of cisplatin (DDP)-resistance is a major challenge that largely limits the efficacy of chemotherapy for osteosarcoma. LncRNA Taurine up-regulated gene 1 (TUG1) is a recently identified oncogenic lncRNA that has been involved in chemo-resistance of various cancers. In this study, over-expression of TUG1 was found in two osteosarcoma cell lines resistant to DDP (Saos-2/DDP, MG-63/DDP). Knockdown of TUG1 inhibited the DDP-resistance and promoted the cytotoxicity and apoptosis induced by DDP in Saos-2/DDP and MG-63/DDP cells. TUG1 knockdown also markedly inhibited the expression level of MET and p-Akt. In conclusion, knockdown of TUG1 suppressed cell growth and increased apoptotic rate under DDP treatment possibly via regulating MET/Akt signalling pathway.

摘要

顺铂（DDP）耐药性的发展是一个主要的挑战，这在很大程度上限制了化疗治疗骨肉瘤的疗效。长链非编码 RNA 牛磺酸上调基因 1（TUG1）是最近发现的一种致癌性长链非编码 RNA，它参与了多种癌症的化疗耐药性。在这项研究中，发现两种对 DDP 耐药的骨肉瘤细胞系（Saos-2/DDP、MG-63/DDP）中 TUG1 的表达上调。TUG1 的敲低抑制了 DDP 耐药性，并促进了 DDP 在 Saos-2/DDP 和 MG-63/DDP 细胞中诱导的细胞毒性和细胞凋亡。TUG1 的敲低也显著抑制了 MET 和 p-Akt 的表达水平。总之，TUG1 的敲低抑制了 DDP 处理下的细胞生长并增加了细胞凋亡率，可能是通过调节 MET/Akt 信号通路。