Research Paper Volume 11, Issue 18 pp 7830—7846
Downregulation of LncRNA-XIST inhibited development of non-small cell lung cancer by activating miR-335/SOD2/ROS signal pathway mediated pyroptotic cell death
- 1 Harbin Medical University, Heilongjiang, China
- 2 Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilong Jiang, China
- 3 Department of Thoracic Surgery, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
- 4 Department of Laboratory, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
- 5 Department of nuclear medicine, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
- 6 Department of Pharmacology and Toxicology, Wright State University, Dayton, OH 45435, USA
received: June 3, 2019 ; accepted: September 14, 2019 ; published: September 25, 2019 ;https://doi.org/10.18632/aging.102291
How to Cite
Copyright © 2019 Liu 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.
LncRNA-XIST participated in the regulation of Non-small cell lung cancer (NSCLC) progression, but the underlying mechanisms are still unclear. This study showed that LncRNA-XIST aberrantly overexpressed in either NSCLC tissues or cell lines comparing to their paired control groups. Knock-down of LncRNA-XIST promoted NSCLC cell apoptosis and inhibited cell proliferation, which were reversed by synergistically treating cells with pyroptosis inhibitor Necrosulfonamide (NSA). In addition, knock-down of LncRNA-XIST also promoted reactive oxygen species (ROS) production and NLRP3 inflammasome activation. In parallel, ROS scavenger N-acetyl cysteine (NAC) abrogated the effects of downregulated LncRNA-XIST on NSCLC cell pyroptosis. Furthermore, miR-335 was the downstream target of LncRNA-XIST and overexpressed LncRNA-XIST increased SOD2 expression levels by sponging miR-335. Mechanistically, miR-335 inhibitor reversed the effects of downregulated LncRNA-XIST on ROS levels and cell pyroptosis, which were abrogated by synergistically knocking down SOD2. Taken together, knock-down of LncRNA-XIST inhibited NSCLC progression by triggering miR-335/SOD2/ROS signal pathway mediated pyroptotic cell death.