MiR-193b regulates breast cancer cell migration and vasculogenic mimicry by targeting dimethylarginine dimethylaminohydrolase 1

Scientific Reports
Julie-Ann HulinArduino A Mangoni

Abstract

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) is responsible for metabolism of an endogenous inhibitor of nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), which plays a key role in modulating angiogenesis. In addition to angiogenesis, tumours can establish a vascular network by forming vessel-like structures from tumour cells; a process termed vasculogenic mimicry (VM). Here, we identified over-expression of DDAH1 in aggressive MDA-MB-231, MDA-MB-453 and BT549 breast cancer cell lines when compared to normal mammary epithelial cells. DDAH1 expression was inversely correlated with the microRNA miR-193b. In DDAH1+ MDA-MB-231 cells, ectopic expression of miR-193b reduced DDAH1 expression and the conversion of ADMA to citrulline. In DDAH1- MCF7 cells, inhibition of miR-193b elevated DDAH1 expression. Luciferase reporter assays demonstrated DDAH1 as a direct target of miR-193b. MDA-MB-231 cells organised into tube structures in an in vitro assay of VM, which was significantly inhibited by DDAH1 knockdown or miR-193b expression. Mechanistically, we found miR-193b regulates cell proliferation and migration of MDA-MB-231 cells, whilst DDAH1 knockdown inhibited cell migration. These studies represent the first eviden...Continue Reading

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Citations

Jun 15, 2018·Cancer Science·Ryota KawaharaSiro Simizu
Feb 20, 2019·Journal of Cellular Physiology·Monireh KhordadmehrBehzad Baradaran
Jan 30, 2020·Frontiers in Oncology·Olga N Hernández de la CruzÁngeles Carlos-Reyes
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Mar 17, 2020·Frontiers in Oncology·Marco A Andonegui-ElgueraJosé Díaz-Chávez
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Aug 8, 2021·Cells·Gabriela Morales-GuadarramaLorenza Díaz

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Methods Mentioned

BETA
RNASeq
transfection
xenografts
PCR
Protein Assay

Software Mentioned

Multi Gauge
GraphPad Prism
GraphPad
ImageJ
TargetScan
IncuCyte
SoftMax Pro
miRanda

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