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SNHG17/miR-384/ELF1 axis promotes cell growth by transcriptional regulation of CTNNB1 to activate Wnt/β-catenin pathway in oral squamous cell carcinoma

Abstract

Increasing evidence proved the abnormal expression of long non-coding RNAs (lncRNAs) in various human malignancies, including oral squamous cell carcinoma (OSCC). Nevertheless, limited explorations concern the role of lncRNA small nucleolar RNA host gene 17 (SNHG17) in OSCC. Herein, SNHG17 was disclosed to be remarkably upregulated in OSCC cell lines and promoted OSCC cell growth. Further mechanistic studies, including DNA/RNA pull down, RIP, ChIP, and luciferase reporter gene assays, were conducted. It was confirmed that Wnt/β-catenin signaling pathway was involved in the SNHG17-mediated OSCC cell growth. Moreover, E74 like ETS transcription factor 1 (ELF1) was identified as the transcription activator of CTNNB1 (β-catenin mRNA) in OSCC. Inspired by competing for endogenous RNAs (ceRNAs) network, we were pleasantly surprised to find that SNHG17 and ELF1 functioned as ceRNAs in OSCC via competitively binding to microRNA-384 (miR-384). By using rescue assays, we revealed that SNHG17 facilitated OSCC cell growth through modulating miR-384/ELF1 axis. Importantly, we certified that ELF1 was indispensable for SNHG17-affected OSCC progression. Collectively, it can be concluded that SNHG17/miR-384/ELF1 axis contributed to OSCC cell growth via promoting CTNNB1 expression, thus activating Wnt/β-catenin signaling pathway.

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Fig. 1: SNHG17 promoted OSCC cell proliferation and inhibited cell apoptosis.
Fig. 2: The involvement of Wnt/β-catenin signaling pathway in SNHG17-mediated OSCC cell proliferation.
Fig. 3: SNHG17 depended on ELF1 to enhance CTNNB1 transcription in OSCC.
Fig. 4: miR-384 might be shared by SNHG17 and ELF1 in OSCC.
Fig. 5: SNHG17 regulated CTNNB1 expression via miR-384/ELF1 axis in OSCC.
Fig. 6: SNHG17 facilitated OSCC cell proliferation by modulating miR-384/ELF1 axis.

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Acknowledgements

Authors deeply appreciate all participants in this study.

Funding

This study was supported by Natural Science Foundation for the Youth of China (No. 81400488), Jilin Provincial Science and Technology Department (No. 20180520058JH), Jilin Province Health and Health Technology Innovation Project (No. 2018J073).

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Correspondence to Chunyan Qiao.

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Qiao, C., Qiao, T., Yang, S. et al. SNHG17/miR-384/ELF1 axis promotes cell growth by transcriptional regulation of CTNNB1 to activate Wnt/β-catenin pathway in oral squamous cell carcinoma. Cancer Gene Ther 29, 122–132 (2022). https://doi.org/10.1038/s41417-021-00294-9

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