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

Rui Chen, Wenjia Xia, Siwei Wang, Youtao Xu, Zhifei Ma, Weizhang Xu, Erbao Zhang, Jie Wang, Tian Fang, Quan'an Zhang, Gaochao Dong, William Chi shing Cho, Patrick C. Ma, Giovanni Brandi, Simona Tavolari, Peter Ujhazy, Giulio Metro, Helmut H. Popper, Rong Yin, Mantang QiuLin Xu

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10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)543-553
Number of pages11
JournalMolecular Therapy - Nucleic Acids
Volume16
DOIs
StatePublished - Jun 7 2019

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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    Chen, R., Xia, W., Wang, S., Xu, Y., Ma, Z., Xu, W., Zhang, E., Wang, J., Fang, T., Zhang, Q., Dong, G., Cho, W. C. S., Ma, P. C., Brandi, G., Tavolari, S., Ujhazy, P., Metro, G., Popper, H. H., Yin, R., ... Xu, L. (2019). Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma. Molecular Therapy - Nucleic Acids, 16, 543-553. https://doi.org/10.1016/j.omtn.2019.04.004