| Popis: |
Background: Single nucleotide polymorphisms (SNPs) and long non-coding RNAs (lncRNAs) have been involved in the process of lung cancer. Following clues given by lung cancer risk-associated SNPs, we aimed to find novel functional lncRNAs as candidate targets in non-small cell lung cancer (NSCLC). Methods: Case-control analyses were performed in 626 cases and 736 controls matched up on sex and age. The lncRNA OSER1-AS1 was identified near a lung cancer risk-associated SNP rs4142441. Kaplan–Meier survival analysis was performed to investigate the association between OSER1-AS1 expression and overall survival. The influence of rs4142441 on the expression level of OSER1-AS1 was confirmed using Luciferase assays. Subsequently, the biological function of OSER1-AS1 was assessed in vitro by cell proliferation, migration, and invasion experiments through gain- and loss-of-function approaches, and in vivo by subcutaneous tumor model and tail vein injection lung metastasis model. ChIP and RIP experiments were carried out to investigate the interaction between transcription factors, RNA-binding proteins, and OSER1-AS1.Results: OSER1-AS1 was down-regulated in tumor tissue and its low expression was significantly associated with poor overall survival among non-smokers in NSCLC patients. Gain- and loss-of-function studies revealed that OSER1-AS1 acted as a tumor suppressor by inhibiting lung cancer cell growth, migration and invasion in vitro. Xenograft tumor assays and 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. Conclusion: 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. |
