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

Research output: Contribution to journalArticle

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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

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Long Noncoding RNA
Carcinogenesis
Adenocarcinoma of lung
RNA Sequence Analysis
cdc Genes
Atlases
Transcriptome
Squamous Cell Carcinoma
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Chen, Rui ; Xia, Wenjia ; Wang, Siwei ; Xu, Youtao ; Ma, Zhifei ; Xu, Weizhang ; Zhang, Erbao ; Wang, Jie ; Fang, Tian ; Zhang, Quan'an ; Dong, Gaochao ; Cho, William Chi shing ; Ma, Patrick C. ; Brandi, Giovanni ; Tavolari, Simona ; Ujhazy, Peter ; Metro, Giulio ; Popper, Helmut H. ; Yin, Rong ; Qiu, Mantang ; Xu, Lin. / Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma. In: Molecular Therapy - Nucleic Acids. 2019 ; Vol. 16. pp. 543-553.
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title = "Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma",
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.",
author = "Rui Chen and Wenjia Xia and Siwei Wang and Youtao Xu and Zhifei Ma and Weizhang Xu and Erbao Zhang and Jie Wang and Tian Fang and Quan'an Zhang and Gaochao Dong and Cho, {William Chi shing} and Ma, {Patrick C.} and Giovanni Brandi and Simona Tavolari and Peter Ujhazy and Giulio Metro and Popper, {Helmut H.} and Rong Yin and Mantang Qiu and Lin Xu",
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month = "6",
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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, WCS, Ma, PC, Brandi, G, Tavolari, S, Ujhazy, P, Metro, G, Popper, HH, Yin, R, Qiu, M & Xu, L 2019, 'Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma', Molecular Therapy - Nucleic Acids, vol. 16, pp. 543-553. https://doi.org/10.1016/j.omtn.2019.04.004

Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma. / Chen, Rui; Xia, Wenjia; Wang, Siwei; Xu, Youtao; Ma, Zhifei; Xu, Weizhang; Zhang, Erbao; Wang, Jie; Fang, Tian; Zhang, Quan'an; Dong, Gaochao; Cho, William Chi shing; Ma, Patrick C.; Brandi, Giovanni; Tavolari, Simona; Ujhazy, Peter; Metro, Giulio; Popper, Helmut H.; Yin, Rong; Qiu, Mantang; Xu, Lin.

In: Molecular Therapy - Nucleic Acids, Vol. 16, 07.06.2019, p. 543-553.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long Noncoding RNA SBF2-AS1 Is Critical for Tumorigenesis of Early-Stage Lung Adenocarcinoma

AU - Chen, Rui

AU - Xia, Wenjia

AU - Wang, Siwei

AU - Xu, Youtao

AU - Ma, Zhifei

AU - Xu, Weizhang

AU - Zhang, Erbao

AU - Wang, Jie

AU - Fang, Tian

AU - Zhang, Quan'an

AU - Dong, Gaochao

AU - Cho, William Chi shing

AU - Ma, Patrick C.

AU - Brandi, Giovanni

AU - Tavolari, Simona

AU - Ujhazy, Peter

AU - Metro, Giulio

AU - Popper, Helmut H.

AU - Yin, Rong

AU - Qiu, Mantang

AU - Xu, Lin

PY - 2019/6/7

Y1 - 2019/6/7

N2 - 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.

AB - 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.

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DO - 10.1016/j.omtn.2019.04.004

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