Single-Nucleotide Polymorphism Rs4142441 And Myc Co-Modulated Long Non-Coding Rna Oser1-As1 Suppresses Non-Small Cell Lung Cancer By Sequestering Elavl1

CANCER SCIENCE(2021)

引用 16|浏览40
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摘要
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.
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关键词
ELAVL1, long non&#8208, coding RNA, miR&#8208, 17&#8208, 5p, non&#8208, small cell lung cancer, OSER1&#8208, AS1
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