Published online Nov 28, 2019. doi: 10.3748/wjg.v25.i44.6495
Peer-review started: October 10, 2019
First decision: November 10, 2019
Revised: November 20, 2019
Accepted: November 23, 2019
Article in press: November 23, 2019
Published online: November 28, 2019
The human microRNA 375 (MIR375) is significantly downregulated in human colorectal cancer (CRC) and we have previously shown that MIR375 is a CRC-associated miRNA. The metadherin (MTDH) is a candidate target gene of MIR375.
To investigate the interaction and function between MIR375 and MTDH in human CRC.
A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression. The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR (qRT-PCR), western blotting, or immunohistochemistry.
MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls. We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways [BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha (PIK3CA)-AKT] in CRC cells. Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha, which further upregulated NFKB1 and RELA expression in CRC cells.
Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression. Thus, MIR375 may be of therapeutic value in treating human CRC.
Core tip: The microRNA 375 (MIR375) is significantly downregulated in human colorectal cancer (CRC) tissues. In this study, we investigated that metadherin (MTDH) is a direct target gene of MIR375 and that MTDH expression levels were upregulated in CRC tissues. Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha expression, which further upregulated NFKB1 and RELA expression in CRC cells. MIR375 also regulate MTDH-mediated BRAF-MAPK and PIK3CA-AKT signal pathways in CRC cells. Consequently, MIR375 regulates cell proliferation, cell migration, and angiogenesis by suppressing MTDH expression in CRC progression.