Single-nucleotide polymorphism rs4142441 and MYC co-modulated long non-coding RNA OSER1-AS1 suppresses non-small cell lung cancer by sequestering ELAVL1.

Abstract

Single‐nucleotide polymorphisms (SNP) and long non‐coding RNAs (lncRNAs) have been involved in the process of lung cancer. Following clues given by lung cancer risk‐associated SNP, we aimed to find novel functional lncRNAs as candidate targets in lung cancer. We identified a lncRNA Oxidative Stress Responsive Serine Rich 1 Antisense RNA 1 (OSER1‐AS1) through a lung cancer risk‐associated SNP rs4142441. OSER1‐AS1 was down‐regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non‐smokers in non‐small cell lung cancer (NSCLC) patients. Gain‐ and loss‐of‐function studies showed that OSER1‐AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and a metastasis mouse model confirmed that OSER1‐AS1 suppressed tumor growth and metastasis in vivo. The promoter of OSER1‐AS1 was repressed by MYC, and the 3′‐end of OSER1‐AS1 was competitively targeted by microRNA hsa‐miR‐17‐5p and RNA‐binding protein ELAVL1. Our results indicated that OSER1‐AS1 exerted tumor‐suppressive functions by acting as an ELAVL1 decoy to keep it away from its target mRNAs. Our findings characterized OSER1‐AS1 as a new tumor‐suppressive lncRNA in NSCLC, suggesting that OSER1‐AS1 may be suitable as a potential biomarker for prognosis, and a potential target for treatment.