Abstract
Non-small cell lung cancer (NSCLC) is a foremost cause of malignancy-associated mortality globally. Recent studies have emphasized long non-coding RNAs (lncRNAs) as important biomarkers with diagnostic and therapeutic potential in regard to NSCLC. This study aimed to elucidate the functional role of lncRNA small nucleolar RNA host gene 4 (SNHG4) in NSCLC. Initially, 50 paired cancerous and noncancerous tissues were obtained from NSCLC patients. Human NSCLC H1299 cells were assayed to evaluate viability, colony formation, invasion, migration, cycle arrest, and apoptosis via Cell Counting Kit-8 (CCK-8), plate clone formation, and transwell invasion assays, as well as a scratch test and flow cytometry. A dual-luciferase reporter gene assay was used to examine lncRNA SNHG4 binding with miR-let-7e and miR-let-7e binding with lysine demethylase 3A (KDM3A). H1299 cells were xenografted into nude mice. lncRNAs SNHG4 and KDM3A were both upregulated in NSCLC tissues. The knockdown of lncRNA SNHG4 or KDM3A inhibited H1299 cell viability, colony formation, invasion, migration, and cycle progression while inducing apoptosis. lncRNA SNHG4 was found to bind to miR-let-7e that negatively targeted KDM3A. KDM3A inhibited p53-K372me1, thus reducing p21 expression. The NSCLC development was inhibited by downregulating lncRNA SNHG4 in nude mice. Taken together, the key findings of the current study demonstrate a novel lncRNA SNHG4/let-7e/KDM3A/p21 axis in NSCLC, highlighting a promising therapeutic target for NSCLC.
Highlights
As a distinct cause of cancer-related deaths worldwide, lung cancer is classified into two major histological subtypes: non-small cell lung cancer (NSCLC) and SCLC.[1]
Upregulated long non-coding RNAs (lncRNAs) small nucleolar RNA host gene 4 (SNHG4) was associated with NSCLC prognosis In order to investigate the oncogenic and prognostic effect of lncRNA SNHG4 in NSCLC, we initially identified the expression of lncRNA SNHG4 in 50 cancerous tissues and matched noncancerous lung tissues via quantitative reverse transcription polymerase chain reaction
These results provided evidence indicating the negative association between lncRNA SNHG4 and the overall survival rate and disease-free survival rate of patients with NSCLC
Summary
As a distinct cause of cancer-related deaths worldwide, lung cancer is classified into two major histological subtypes: non-small cell lung cancer (NSCLC) and SCLC.[1]. A more in-depth understanding of the molecular mechanisms underlying NSCLC is of great significance in order to identify more effective prevention strategies and therapeutic methods for NSCLC
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