Mechanosensitive pathways are regulated by mechanosensitive miRNA clusters in endothelial cells

Area of Science:

• Molecular Biology
• Cellular Mechanobiology
• Biochemistry

Background:

• Mechanotransduction, the process by which cells convert mechanical stimuli into biochemical signals, is vital in (patho-)physiology.
• The intricate regulation of mechanotransduction has been a subject of extensive research, with a growing interest in post-transcriptional gene regulation.
• Small non-coding RNAs, specifically microRNAs (miRNAs), are increasingly recognized for their role in modulating gene expression.

Purpose of the Study:

• To comprehensively review the existing literature on the role of small non-coding miRNAs in regulating mechanotransduction.
• To investigate the specific contribution of miRNA families and miRNA clusters in the context of mechanotransduction.
• To propose and support a novel hypothesis regarding the predominant role of miRNA clusters in mechanotransduction regulation.

Main Methods:

• Comprehensive literature evaluation focusing on miRNA regulation of mechanotransduction.
• Analysis of miRNA families and miRNA clusters, considering their structural impact on mRNA regulation.
• Integration of existing literature findings with data from a previously conducted study on mechanotransduction.

Main Results:

• miRNA-mediated regulation of mRNA is complex, influenced by relative concentrations and competitive binding.
• Overarching miRNA structures, namely families and clusters, offer a mechanism to counteract competitive binding.
• Both literature evidence and the study's data strongly suggest that miRNA clusters predominantly regulate mechanotransduction, affecting approximately 65% of relevant signaling pathways.

Conclusions:

• A novel regulatory mode for mechanotransduction, primarily driven by miRNA clusters, is proposed.
• This discovery provides significant insights into the molecular mechanisms underlying mechanotransduction.
• The findings open new therapeutic avenues for conditions involving dysregulated mechanotransduction, such as atherosclerosis.