Pathology and Oncology Research, 2019. 25(3), 953-959, DOI: https://doi.org/10.3390/cancers11101613

MicroRNA 196B regulates HOXA5, HOXB6 and GLTP expression levels in colorectal cancer cells

Soo-Cheon Chae, Ji-Su Mo;Young-Ran Park

Abstract

The human microRNA 452 (MIR452) was identified as a colorectal cancer (CRC)-associatedmicro RNA (miRNA) by miRNA expression profiling of human CRC tissues versus normal colorectaltissues. It was significantly up-regulated in human CRC tissues. However, the functional mechanismsof MIR452 and its target genes in CRC remain unclear. We identified 27 putative MIR452 target genes,and found that the vascular endothelial growth factor A (VEGFA) was a direct target gene of MIR452.Both cellular and extracellular VEGFA levels were significantly downregulated in CRC cells upon theirtransfection with MIR452 or siVEGFA. VEGFA expression was frequently downregulated in humanCRC tissues in comparison with that in their healthy counterparts. We showed that MIR452 regulatedthe expression of genes in the VEGFA-mediated signal transduction pathways vascular endothelialgrowth factor receptor 1 (VEGFR2)–mitogen-activated protein kinase (MAPK) and VEGFR2–SRCproto-oncogene non-receptor tyrosine kinase (SRC) in CRC cells. Immunohistological analyses ofxenografted MIR452-overexpressing CRC cells in mice showed that MIR452 regulated cell proliferationand angiogenesis. Furthermore, aortic ring angiogenesis assay in rats clearly showed that the numberof microvessels formed was significantly reduced by MIR452 transfection. Our findings suggestthat MIR452 regulates cell proliferation, cell migration, and angiogenesis by suppressing VEGFAexpression in early CRC progression; therefore, MIR452 may have therapeutic value in relation tohuman CRC.

• DOI: https://doi.org/10.3390/cancers11101613
• ISBN or ISSN: 1219-4956

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.