miRNA-708 functions as a tumor suppressor in colorectal cancer by targeting ZEB1 through Akt/mTOR signaling pathway

摘要

Background: Colon cancer, or colorectal cancer (CRC), is a type of cancer that develops from large bowel. Previous data has demonstrated that microRNAs (miRNAs) may be involved in the formation and progression of CRC. The deregulation of miR-708 has been identified in multiple types of cancer. However, to the best of our knowledge, there are no data concerning the expression and role of miR-708 in CRC. Methods: In this study, RT-PCR and Flow Cytometry were used to examine the expression and role of miR-708 and ZEB1 in proliferation and apoptosis. Transwell was used to examine the role of miR-708 and ZEB1 in invasion and migration. Western blot and qRT-PCR were conducted to determine the alteration of protein and miR-708 levels, respectively. Results: MiR-708 was significantly downregulated in CRC tissues and cell lines. The restoration of the expression of miR-708 suppressed cell proliferation, induced apoptosis, and reduced metastasis in CRC in vitro. Additionally, bioinformatics analysis predicted ZEB1 as a novel target gene of miR-708. Furthermore, ZEB1 was upregulated in CRC, which was negatively correlated with miR-708 expression. Further studies showed that the overexpression of miR-708 and silence of ZEB1 inhibited stage of CRC via inhibiting AKT/mTOR signaling pathway in CRC cells. Conclusion: Taken together, these results indicate that miR-708 plays an important role in suppressing the development of CRC by directly targeting ZEB1 through AKT/mTOR signaling pathway, suggesting that miR-708 is a novel, effective therapeutic target for treating patients with CRC.