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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

Jinglei Liu1,2, Lei Yao1,3, Mingyan Zhang1,4, Ji Jiang1,5, Maopeng Yang1,2, Yue Wang6
  • 1Harbin Medical University, Heilongjiang, China
  • 2Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Heilong Jiang, China
  • 3Department of Thoracic Surgery, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
  • 4Department of Laboratory, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
  • 5Department of nuclear medicine, The Third Affiliated Hospital of Harbin Medical University, Heilongjiang, China
  • 6Department of Pharmacology and Toxicology, Wright State University, Dayton, OH 45435, USA
Received: June 3, 2019Accepted: September 14, 2019Published: September 25, 2019

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.

Abstract

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.