Silencing of LncRNA SNHGI6 Downregulates Cyclin D1 Through Upregulating miR-17-5p

• Published in: Cancer management and research 2021-02, Vol.13, p.1831
• Main Authors: Wang, Qiuling, Han, Jingxin, Xu, Pu, Jian, Xinchun, Huang, Xieshan, Liu, Deyu
• Format: Article
• Language: English
• Subjects: Analysis; Apoptosis; Cancer; Development and progression; Genetic aspects; Genetic transcription; Health aspects; MicroRNA; Phenotype; Squamous cell carcinoma
• ISSN: 1179-1322; 1179-1322
• DOI: 10.2147/CMAR.S298236

Background: Targeting the long non-coding RNAs (LncRNAs)-microRNAs (miRNAs)mRNA competing endogenous RNA (ceRNA) networks has been proved as an effective strategy to treat multiple cancers, including oral squamous cell carcinoma (OSCC). Based on this, the present study identified a novel LncRNA SNHG16/miR-17-5p/CCND1 signaling pathway that played an important role in regulating the pathogenesis of OSCC. Methods: The expression levels of cancer-associated genes were examined by Real-Time qPCR and Western Blot at transcriptional and translated levels, respectively. CCK-8 assay was performed to determine cell proliferation, and cell apoptosis ratio was measured by the Annexin V-FITC/PI double staining assay. Transwell assay was performed to examine cell migration, and dual-luciferase reporter gene system assay was used to validate the ceRNA networks. Results: LncRNA SNHG16 and CCND1 were upregulated, while miR-17-5p was downregulated in OSCC tissues and cell lines, compared to their normal counterparts. Also, miR17-5p negatively correlated with both LncRNA SNHG16 and CCND1 mRNA, but LncRNA SNHG16 was positively relevant to CCND1 mRNA in OSCC tissues. By performing the gain- and loss-of-function experiments, we noticed that LncRNA SNHG16 overexpression aggravated the malignant phenotypes, such as cell proliferation, viability, migration and epithelial-mesenchymal transition (EMT) in OSCC cells, while LncRNA SNHG16 knockdown had opposite effects. Furthermore, our dual-luciferase reporter gene system evidenced that LncRNA SNHG16 sponged miR-17-5p to upregulate CCND1 in OSCC cells, and the inhibiting effects of LncRNA SNHG16 ablation on OSCC progression were abrogated by both downregulating miR-17-5p and overexpressing CCND1. Finally, the xenograft tumorbearing mice models were established, and our data validated that LncRNA SNHG16 served as an oncogene to promote tumorigenicity of OSCC cells in vivo. Conclusion: Taken together, targeting the LncRNA SNHG16/miR-17-5p/CCND1 axis hindered the development of OSCC, and this study provided potential diagnostic and therapeutic biomarkers for OSCC in clinic. Keywords: oral squamous cell carcinoma, competing endogenous RNA, LncRNA SNHG16, MiR-17-5p, cyclin D1