1. Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma
- Author
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Erbao Zhang, Zhifei Ma, Peter Ujhazy, Mantang Qiu, Quan'an Zhang, Siwei Wang, Youtao Xu, Rui Chen, Patrick C. Ma, Lin Xu, Jie Wang, Helmut Popper, W. Xu, Tian Fang, William C. Cho, Giovanni Brandi, Gaochao Dong, Wenjia Xia, Simona Tavolari, Giulio Metro, Rong Yin, and Chen R, Xia W, Wang S, Xu Y, Ma Z, Xu W, Zhang E, Wang J, Fang T, Zhang Q, Dong G, Cho WC, Ma PC, Brandi G, Tavolari S, Ujhazy P, Metro G, Popper HH, Yin R, Qiu M, Xu L.
- Subjects
0301 basic medicine ,Biology ,medicine.disease_cause ,Article ,Transcriptome ,03 medical and health sciences ,0302 clinical medicine ,lncRNA ,Drug Discovery ,medicine ,E2F1 ,Gene ,Gene knockdown ,SBF2-AS1 ,Competing endogenous RNA ,WGCNA ,lcsh:RM1-950 ,ceRNA ,medicine.disease ,lung adenocarcinoma ,Long non-coding RNA ,tumorigenesis ,030104 developmental biology ,lcsh:Therapeutics. Pharmacology ,030220 oncology & carcinogenesis ,Cancer research ,Molecular Medicine ,Adenocarcinoma ,Carcinogenesis - Abstract
Emerging evidence demonstrates that long non-coding RNAs (lncRNAs) are deeply involved in the development of various cancers. This study identified that SBF2-AS1, an early-stage-specific lncRNA, is critical for the tumorigenesis of lung adenocarcinoma (LUAD). We first analyzed LUAD transcriptome data from The Cancer Genome Atlas and the GEO database by weighted gene co-expression network analysis (WGCNA). Five early LUAD-specific lncRNAs were filtered out, and only SBF2-AS1 was upregulated in LUAD. High expression of SBF2-AS1 indicates poor survival of LUAD, especially the early-stage LUAD, but not lung squamous cell carcinoma. SBF2-AS1 promotes LUAD cells proliferation in vitro, and RNA-sequencing data shows that many cell-cycle-related genes were downregulated after SBF2-AS1 knockdown. Mechanically, SBF2-AS1 could competitively bind with miR-338-3p and miR-362-3p to increase E2F1 expression. Finally, we show that the SBF2-AS1-miR-338-3p/362-3p-E2F1 axis could promote LUAD tumorigenesis in vitro and in vivo. Our study demonstrates that SBF2-AS1, an early-stage-specific lncRNA, promotes LUAD tumorigenesis by sponging miR-338-3p and miR-362-3p and increasing E2F1 expression. The SBF2-AS1-miR-338-3p/362-3p-E2F1 regulatory axis may serve as a prognostic marker and potential therapeutic target for LUAD. Keywords: WGCNA, lung adenocarcinoma, tumorigenesis, ceRNA, SBF2-AS1, lncRNA
- Published
- 2019