Research Paper Volume 12, Issue 6 pp 4711—4726
Silencing of lncRNA XIST inhibits non-small cell lung cancer growth and promotes chemosensitivity to cisplatin
- 1 Department of Thoracic Surgery, Peking Union Medical College Hospital, Wangfujing, Dongcheng, Beijing 100730, P.R. China
- 2 Beijing 100biotech Co., Ltd., Beijing 100006, China
Received: September 27, 2019 Accepted: December 25, 2019 Published: March 25, 2020https://doi.org/10.18632/aging.102673
How to Cite
Copyright © 2020 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Long noncoding RNAs (lncRNAs) play critical roles in tumour progression and metastasis. Emerging evidence indicates that the lncRNA X inactive-specific transcript (XIST) is dysregulated in several tumor types, including non-small cell lung cancer (NSCLC). However, in NSCLC and other cancers the oncogenic mechanism of XIST remains incompletely understood. Here, we confirmed that XIST is upregulated in human NSCLC specimens, and is especially overexpressed in tumors previously treated with cisplatin (cis-diamminedichloroplatinum(II); DDP). In vitro, XIST knockdown inhibited NSCLC cell growth and promoted DDP chemosensitivity by stimulating apoptosis and pyroptosis. Moreover, XIST’s oncogenic effects and ability to promote DDP chemoresistance were largely related to its binding to the TGF-β effector SMAD2, which inhibited its translocation to the nucleus and prevented the transcription of p53 and NLRP3, crucial regulators of apoptosis and pyroptosis, respectively. Using DDP-resistant NSCLC cells, mouse xenograft studies verified the oncogenic function of XIST and its ability to inhibit programmed cell death, thereby mediating DDP chemoresistance. These findings suggest that XIST expression may serve as a novel biomarker to predict DDP treatment efficacy, and may help in the design of new therapies to circumvent DDP chemoresistance in NSCLC and other tumor types.