Objective: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Small nucleolar RNA host gene 6 (SNHG6) was reported to function as an oncogene in a number of cancers. Here, we aimed to further explore the roles and molecular mechanism of SNHG6 in CRC metastasis.
Methods: The expression levels of SNHG6, miR-26a, and enhancer of zeste homolog 2 (EZH2) mRNA were assessed by quantification real-time PCR in CRC tissues and cell lines. Western blot analysis was performed to determine the levels of E-cadherin, Snail, Vimentin, N-cadherin, and EZH2. Cell migration and invasion capacities were detected by transwell assay. Dual-luciferase reporter assay or RNA Immunoprecipitation assay was employed to verify the interaction between SNHG6 and miR-26a, or EZH2 and miR-26a.
Results: Our data indicated that SNHG6 and EZH2 mRNA were upregulated, and miR-26a was downregulated in CRC tissues and cell lines. SNHG6 knockdown suppressed the migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells. Moreover, SNHG6 binded to miR-26a and repressed miR-26a expression. EZH2 was a direct target of miR-26a, and it was regulated by SNHG6/miR-26a. MiR-26a inhibitor undermined the effect of SNHG6 knockdown on cell migration, invasion, and EMT. Additionally, EZH2 antagonized the effect of miR-26a on cell migration, invasion, and EMT in CRC cells.
Conclusion: SNHG6 knockdown suppressed cell migration, invasion, and EMT at least partly by sponging miR-26a and regulating EZH2 expression in CRC cells, providing a strategy for blocking CRC metastasis.
Keywords: small nucleolar RNA host gene 6 (SNHG6), miR-26a, enhancer of zeste homolog 2 (EZH2), epithelial-mesenchymal transition (EMT)