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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

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Published on: March 30, 2019

The decrease of mineralcorticoid receptor drives angiogenic pathways in colorectal cancer.

Laura Tiberio¹, Riccardo Nascimbeni, Vincenzo Villanacci

¹Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. tiberio@med.unibs.it

|April 5, 2013

Summary

Low mineralocorticoid receptor (MR) expression in colorectal cancer (CRC) promotes tumor growth by increasing blood vessel formation (angiogenesis). Activating MR may inhibit angiogenesis and improve patient survival in CRC.

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Area of Science:

Oncology
Molecular Biology
Pathology

Background:

Angiogenesis is vital for tumor growth and progression.
Reduced mineralocorticoid receptor (MR) expression is observed in several cancers, including colorectal cancer (CRC), and linked to poorer outcomes.
Decreased MR expression in CRC may contribute to angiogenesis and reduced patient survival.

Purpose of the Study:

To investigate the correlation between MR expression, tumor microvascular density, and patient survival in colorectal cancer.
To determine the role of MR in regulating angiogenesis in an in vitro CRC model.

Main Methods:

Analysis of tumor MR expression, microvascular density, and survival data in a cohort of CRC patients.
In vitro study using HCT116 colon cancer cells engineered to re-express MR.
Assessment of VEGFA and VEGF receptor 2/KDR mRNA levels following MR activation with aldosterone or natural serum steroids.

Main Results:

In CRC patients, lower MR expression correlated with higher microvascular density and poorer survival.
In engineered HCT116 cells, MR activation significantly inhibited VEGFA and VEGF receptor 2/KDR mRNA expression.
MR activation suppressed both dysregulated and hypoxia-induced VEGFA mRNA expression.

Conclusions:

Decreased MR expression in colorectal cancer is associated with increased angiogenesis and reduced patient survival.
MR activation can inhibit angiogenesis in CRC by downregulating VEGFA and its receptor KDR.
Targeting MR may represent a therapeutic strategy to reduce angiogenesis and improve outcomes in colorectal cancer.