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.
Highlights
Non-small cell lung cancer (NSCLC) is one of the most common lung associated cancer [1], which seriously endangered the health of human beings
The results showed that LncRNA-XIST was most significantly overexpressed in NSCLC tissues comparing to the adjacent normal tissues (Figure 1A), which were further validated by the Real-Time qPCR results from additional 30 NSCLC patients (Figure 1B)
The Pan-cancer analysis results showed that lung adenocarcinoma patients with higher LncRNA-XIST levels had comparatively worse prognosis and shorter survival time eventhough without statistical significance (Figure 1E), further Kaplan-Meier analysis validated that the percent survival was significantly higher in patients with low-expressed LncRNA-XIST comparing to their counterparts (Figure 1F)
Summary
Non-small cell lung cancer (NSCLC) is one of the most common lung associated cancer [1], which seriously endangered the health of human beings. Longnoncoding RNAs (lncRNAs) was closely related with the development of multiple cancers, such as bladder cancer [3], gastric cancer [4], ovarian cancer [5] and NSCLC [6]. LncRNA LINC-PINT inhibited NSCLC progression by targeting miR-218-5p/PDCD4 [6] and LncRNA AWPPH promoted NSCLC cell proliferation by activating Wnt/β-catenin signaling pathway [7]. LncRNA-XIST served as an oncogene in various cancers [8, 9] and promoted NSCLC development [10,11,12]. LncRNA-XIST promoted NSCLC cell proliferation, invasion and metastasis [13]
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