microRNA-374a suppresses colon cancer progression by directly reducing CCND1 to inactivate the PI3K/AKT pathway
research target：microRNA-374a
Periodicals：Oncotarget
IF：5.168
Cooperative Unit：Southern Medical University、Guangzhou Medical University
Time of publication：May 12, 2016
Summary
microRNA-374a (miR-374a) exhibits oncogenic functions in various tumor types. Here we report that miR-374a suppresses proliferation, invasion, migration and intrahepatic metastasis in colon adenocarcinoma cell lines HCT116 and SW620. Notably, we detected that PI3K/AKT signaling and its downstream cell cycle factors including c-Myc, cyclin D1 (CCND1), CDK4 and epithelial-mesenchymal transition (EMT)-related genes including ZEB1, N-cadherin, Vimentin, Slug, and Snail were all signifcantly downregulated after miR-374a overexpression. Conversely, cell cycle inhibitors p21 and p27 were upregulated. Expression of E-cadherin was only decreased in HCT116, without any obvious differences observed in SW620 cells. Furthermore, luciferase reporter assays confrmed that miR-374a could directly reduce CCND1. Interestingly, when CCND1 was silenced or overexpressed, levels of pPI3K, pAkt as well as cell cycle and EMT genes were respectively downregulated or upregulated. We examined miR-374a levels by in situ hybridization and its correlation with CCND1 expression in CRC tumor tissues. High miR-374a expression with low level of CCND1 was protective factor in CRC. Together these fndings indicate that miR-374a inactivates the PI3K/AKT axis by inhibiting CCND1, suppressing of colon cancer progression.
Colorectal cancer is the most common gastrointestinal tumor with increasing incidence and mortality. The study found that microRNA downregulation may induce the pathogenesis of colorectal cancer. miR-374a can promote or inhibit the development of human cancer. Some scholars believe that miR-374a can induce the EMT process of breast cancer and promote the proliferation of gastric cancer cells. The down-regulation of miR-374a in colorectal cancer can reduce the mortality of colorectal cancer patients. This article aims to deeply explore the biological function of miR-374a in colorectal cancer, the pathways it may be involved in, and its mechanism.
Partial results of cooperation
1、miR-374a overexpresssion inhibits proliferation, invasion and migration in vitro and in vivo.
2、miR-374a is a negative regulator of PI3K/AKT signaling and suppresses cell cycle, invasion and migration relevant genes.
3、As a target of miR-374a, CCND1 exerts feedback on PI3K/AKT pathway and downstream cell cycle and EMT genes.
4、The correlation between miR-374a and CCND1 in colon cancer tissues and their clinical significance.
References
Chen Y, Jiang J, Zhao M et al. microRNA-374a suppresses colon cancer progression by directly reducing CCND1 to inactivatethe PI3K/AKT pathway.
