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c-Myc induced upregulation of long non-coding RNA SNHG16 enhances progression and carcinogenesis in oral squamous cell carcinoma

Cancer Gene Therapy volume 26, pages 400–410 (2019)Cite this article

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Abstract

Small nucleolar RNA host gene 16 (SNHG16) has been documented to be involved in the pathogenesis of human cancers. Here, we elucidated the biological roles and regulatory mechanism of SNHG16 in the pathogenesis of oral squamous cell carcinoma (OSCC). In this paper, we found that c-Myc and SNHG16 were overexpressed in OSCC tissues and cell lines compared with normal tissues and normal human oral keratinocytes cells. There was a notable positive correlation between SNHG16 and c-Myc expression in OSCC tissues. c-Myc silencing by either shRNA c-Myc or by 10058-F4 (c-Myc inhibitor) resulted in a dose-dependent reduction in SNHG16 levels in CAL-27 and TSCCA cells; conversely, upregulation of c-Myc by pcDNA c-Myc markedly increased SNHG16 expression. Depletion of SNHG16 in CAL-27 cells strikingly inhibited cell proliferation, migration and invasion, as indicated by downregulation of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase (MMP)-2 and MMP-9. Moreover, depletion of SNHG16 induced cell apoptosis and inhibited epithelial-to-mesenchymal transition as indicated by induction of cleaved caspase-3 and epithelial cadherin (E-cadherin) along with reduction of N-cadherin and Snail. Intriguingly, c-Myc knockdown led to the similar functional effects as that of SNHG16 knockdown in TSCCA cells. However, these changes caused by c-Myc knockdown were abrogated by SNHG16 overexpression. Knockdown of SNHG16 conspicuously repressed tumor growth in nude mice. Similarly, silencing of c-Myc markedly inhibited tumor growth and reduced SNHG16 expression in nude mice. Moreover, overexpression of SNHG16 blocked the inhibitory effect of c-Myc silencing on tumor growth in vivo. Thus, we conclude that c-Myc-induced upregulation of SNHG16 enhances progression and carcinogenesis in OSCC.

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Authors and Affiliations

  1. Department of Stomatology, The First People’s Hospital of Shangqiu, Shangqiu, 476100, Henan, China

    Shangfeng Li & Shengkai Zhang

  2. Department of Head and Neck Surgery, Hunan Cancer Hospital, Changsha, 410006, Hunan, China

    Jie Chen

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Correspondence to Shangfeng Li.

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Li, S., Zhang, S. & Chen, J. c-Myc induced upregulation of long non-coding RNA SNHG16 enhances progression and carcinogenesis in oral squamous cell carcinoma. Cancer Gene Ther 26, 400–410 (2019). https://doi.org/10.1038/s41417-018-0072-8

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