Silencing of lncRNA XIST inhibits non-small cell lung cancer growth and promotes chemosensitivity to cisplatin
| Autor: | Chao Gao, Yushang Cui, Xiaoyun Zhou, Luo Zhao, Xiaohui Xu, Zhenju Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Aging
Programmed cell death endocrine system diseases Antineoplastic Agents Smad2 Protein Biology NSCLC Metastasis lncRNA Carcinoma Non-Small-Cell Lung Tumor Cells Cultured medicine Humans Gene silencing XIST Cisplatin Gene knockdown pyroptosis apoptosis Pyroptosis chemoresistance Cell Biology medicine.disease Gene Expression Regulation Neoplastic Cancer research RNA Long Noncoding Research Paper medicine.drug Transforming growth factor |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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