Reduced microRNA 375 in colorectal cancer upregulates metadherin-mediated signaling.

Abstract:

BACKGROUND: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. AIM:To investigate the interaction and function between MIR375 and MTDH in human CRC. METHODS: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. RESULTS: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. CONCLUSION: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.

journal_name

World J Gastroenterol

authors

Han SH,Mo JS,Park WC,Chae SC

doi

10.3748/wjg.v25.i44.6495

subject

Has Abstract

pub_date

2019-11-28 00:00:00

pages

6495-6507

issue

44

eissn

1007-9327

issn

2219-2840

journal_volume

25

pub_type

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