Background: Long noncoding RNAs (lncRNAs) have been identified as a novel class of regulators implicated in diverse biological processes in human cancers. Currently, evidence have shown that SNHG6, a cancer-associated lncRNA, exerts critical functions in gastric cancer and hepatocellular carcinoma; however, its role in colorectal cancer (CRC) remains unclear.
Methods: The expression of SNHG6 was determined by quantitative real-time PCR in CRC tissues and cells. SNHG6 was downregulated by using RNAi technology. Cell proliferation was examined by MTT and clone formation assays. Cell migration and invasion were determined by wound healing and transwell assays. Fluorescence in situ hybridization assays were performed to examine subcellular localization of SNHG6 in CRC cells. Fluorescence reporter and Western blot assays were used to explore the potential mechanisms of SNHG6 in CRC progression.
Results: In this study, we found that SNHG6 was significantly upregulated in CRC tissues and cell lines, compared with normal tissues and normal colorectal epithelial cell line NCM460, respectively. High expression of SNHG6 was positively correlated with tumor size, advanced TNM stage, and distant metastasis. Survival analyses revealed that SHNG6 was significantly associated with poor clinical outcomes and could serve as an independent prognostic factor. Loss-of-function studies demonstrated that SNHG6 knockdown inhibited CRC cell proliferation, induced G0/G1 arrest, promoted apoptosis, suppressed CRC cell migration and invasion, and restrained tumor growth. Mechanistic investigations showed that SNHG6 acted as a competing endogenous RNA for miR-181a-5p and attenuated the inhibitory effect of miR-181a-5p on E2F5.
Conclusion: Taken together, these results demonstrated that SNHG6 plays a crucial role in CRC progression via miR-181a-5p/E2F5 axis. Therefore, SNHG6 may serve as a prognostic and therapeutic biomarker in CRC.
Keywords: SNHG6, colorectal cancer, miR-181a-5p, E2F5, proliferation