Theranostics 2020; 10(23):10823-10837. doi:10.7150/thno.47830 This issue Cite

Research Paper

LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network

Yin Zhang1,2*, Yong-Xin Huang1,2*, Dan-Lan Wang1,2, Bing Yang1,2, Hai-Yan Yan1, Le-Hang Lin1,2, Yun Li1,2, Jie Chen1,2, Li-Min Xie1,2, Yong-Sheng Huang1,2, Jian-You Liao1,2, Kai-Shun Hu1,2, Jie-Hua He1,2, Phei Er Saw1,2, Xiaoding Xu1,2, Dong Yin1,2✉

1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P. R. China.
2. Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, P. R. China.
*These authors contributed equally to this work.

Citation:
Zhang Y, Huang YX, Wang DL, Yang B, Yan HY, Lin LH, Li Y, Chen J, Xie LM, Huang YS, Liao JY, Hu KS, He JH, Saw PE, Xu X, Yin D. LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network. Theranostics 2020; 10(23):10823-10837. doi:10.7150/thno.47830. https://www.thno.org/v10p10823.htm
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Abstract

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Rationale: The forkhead box A1 (FOXA1) is a crucial transcription factor in initiation and development of breast, lung and prostate cancer. Previous studies about the FOXA1 transcriptional network were mainly focused on protein-coding genes. Its regulatory network of long non-coding RNAs (lncRNAs) and their role in FOXA1 oncogenic activity remains unknown.

Methods: The Cancer Genome Atlas (TCGA) data, RNA-seq and ChIP-seq data were used to analyze FOXA1 regulated lncRNAs. RT-qPCR was used to detect the expression of DSCAM-AS1, RT-qPCR and Western blotting were used to determine the expression of FOXA1, estrogen receptor α (ERα) and Y box binding protein 1 (YBX1). RNA pull-down and RIP-qPCR were employed to investigate the interaction between DSCAM-AS1 and YBX1. The effect of DSCAM-AS1 on malignant phenotypes was examined through in vitro and in vivo assays.

Results: In this study, we conducted a global analysis of FOXA1 regulated lncRNAs. For detailed analysis, we chose lncRNA DSCAM-AS1, which is specifically expressed in lung adenocarcinoma, breast and prostate cancer. The expression level of DSCAM-AS1 is regulated by two super-enhancers (SEs) driven by FOXA1. High expression levels of DSCAM-AS1 was associated with poor prognosis. Knockout experiments showed DSCAM-AS1 was essential for the growth of xenograft tumors. Moreover, we demonstrated DSCAM-AS1 can regulate the expression of the master transcriptional factor FOXA1. In breast cancer, DSCAM-AS1 was also found to regulate ERα. Mechanistically, DSCAM-AS1 interacts with YBX1 and influences the recruitment of YBX1 in the promoter regions of FOXA1 and ERα.

Conclusion: Our study demonstrated that lncRNA DSCAM-AS1 was transcriptionally activated by super-enhancers driven by FOXA1 and exhibited lineage-specific expression pattern. DSCAM-AS1 can promote cancer progression by interacting with YBX1 and regulating expression of FOXA1 and ERα.

Keywords: FOXA1, lncRNAs, super-enhancer, lung adenocarcinoma, breast cancer, ERα


Citation styles

APA
Zhang, Y., Huang, Y.X., Wang, D.L., Yang, B., Yan, H.Y., Lin, L.H., Li, Y., Chen, J., Xie, L.M., Huang, Y.S., Liao, J.Y., Hu, K.S., He, J.H., Saw, P.E., Xu, X., Yin, D. (2020). LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network. Theranostics, 10(23), 10823-10837. https://doi.org/10.7150/thno.47830.

ACS
Zhang, Y.; Huang, Y.X.; Wang, D.L.; Yang, B.; Yan, H.Y.; Lin, L.H.; Li, Y.; Chen, J.; Xie, L.M.; Huang, Y.S.; Liao, J.Y.; Hu, K.S.; He, J.H.; Saw, P.E.; Xu, X.; Yin, D. LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network. Theranostics 2020, 10 (23), 10823-10837. DOI: 10.7150/thno.47830.

NLM
Zhang Y, Huang YX, Wang DL, Yang B, Yan HY, Lin LH, Li Y, Chen J, Xie LM, Huang YS, Liao JY, Hu KS, He JH, Saw PE, Xu X, Yin D. LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network. Theranostics 2020; 10(23):10823-10837. doi:10.7150/thno.47830. https://www.thno.org/v10p10823.htm

CSE
Zhang Y, Huang YX, Wang DL, Yang B, Yan HY, Lin LH, Li Y, Chen J, Xie LM, Huang YS, Liao JY, Hu KS, He JH, Saw PE, Xu X, Yin D. 2020. LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network. Theranostics. 10(23):10823-10837.

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