Research Of MiR-375Regulatory Mechanisms In Colorectal Cancer

Colorectal cancer(CRC) is the fourth leading cause of cancer-related deaths in China. Early diagnosis of CRC in the pre-clinical state could down-stage the tumors and increase survival.MicroRNAs(miRNA) play a key role in the occurrence and metasis of various cancers. The levels of miRNAs profoundly differed between patients and healthy control, which indicating a great potential of miRNA as predictive and prognostic markers for cancer. In this study, miR-375was found selectively down-regulated in CRC tissues than that in para-carcinoma tissues. However, it remains unclear whether or not miR-375involved in the tumor invasion and metasis of CRC, and the underlying mechanisms mediating miR-375regulation needs to be elucidate. Therefore, we screened various databases for miR-375targeted genes and related signal pathways, JAK/STAT3, MAP3K8/ERK and ATG7/LCIII pathways were identified as predicted targets. To further validate the targeting pathways, miR-375was over-expressed respectively in CRC cell line HT29, HCT116and Caco2. we detected the protein levels of JAK2and MAP3K8were down-regulated, as well as the downstream STAT3and pERK1/2. but miR-375over-expression did not change ATG7level. Moreover, cell proliferation assay showed that miR-375inhibited cell proliferation and migration in certain extent. The tumorigenicity experiments in nude mice demonstrated that all mice in control group formed tumors in15days, and the tumor volume was increased with time, in contrast, no tumor formation in miR-375injected mice even in35days.In conclusion, miR-375is down-regulated in colorectal cancer. It regulate cell proliferation and migration by targeting JAK2/STAT3and MAP3K8/ERK, but not ATG7/LCIII signaling pathway. Our findings may shed light on the clinical applications of miR-375as a diagnostic marker and targeted treatment molecule in colorectal cancer.