4.7 Article

Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma

Journal

MOLECULAR THERAPY-NUCLEIC ACIDS
Volume 16, Issue -, Pages 543-553

Publisher

CELL PRESS
DOI: 10.1016/j.omtn.2019.04.004

Keywords

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Funding

  1. National Natural Science Foundation of China [81372321, 81472200, 81572261, 81702377, 81702256]
  2. Innovation Capability Development Project of Jiangsu Province [BM2015004]
  3. Project of Jiangsu Provincial Medical Talent [ZDRCA2016033]
  4. Natural Science Foundation of Beijing [7182169]
  5. Key Project of Cutting-edge Clinical Technology of Jiangsu Province [BE2016797]
  6. Postdoctoral Fellowship of the Peking-Tsinghua Center for Life Sciences

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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-stagespecific 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.

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