Herault Sean, Naser Jarka, Carassiti Daniele, Chooi K Yean, Nikolopoulou Rosa, Font Marti Llopart, Patel Miten, Pedrigi Ryan, Krams Rob
School of Engineering and Materials Science, Queen Mary University of London, Room 2.14, London, UK.
NHLI, Imperial College London, London, UK.
Biophys Rev. 2021 Oct 23;13(5):787-796. doi: 10.1007/s12551-021-00839-0. eCollection 2021 Oct.
Shear stress is known to affect many processes in (patho-) physiology through a complex, multi-molecular mechanism, termed mechanotransduction. The sheer complexity of the process has raised questions how mechanotransduction is regulated. Here, we comprehensively evaluate the literature about the role of small non-coding miRNA in the regulation of mechanotransduction. Regulation of mRNA by miRNA is rather complex, depending not only on the concentration of mRNA to miRNA, but also on the amount of mRNA competing for a single mRNA. The only mechanism to counteract the latter factor is through overarching structures of miRNA. Indeed, two overarching structures are present miRNA families and miRNA clusters, and both will be discussed in details, regarding the latest literature and a previous conducted study focussed on mechanotransduction. Both the literature and our own data support a new hypothesis that miRNA-clusters predominantly regulate mechanotransduction, affecting 65% of signalling pathways. In conclusion, a new and important mode of regulation of mechanotransduction is proposed, based on miRNA clusters. This finding implicates new avenues for treatment of mechanotransduction and atherosclerosis.
已知剪切应力通过一种复杂的多分子机制（称为机械转导）影响（病理）生理学中的许多过程。该过程的极度复杂性引发了关于机械转导如何被调节的问题。在这里，我们全面评估了关于小非编码miRNA在机械转导调节中作用的文献。miRNA对mRNA的调节相当复杂，不仅取决于mRNA与miRNA的浓度，还取决于竞争单个mRNA的mRNA数量。抵消后一个因素的唯一机制是通过miRNA的总体结构。事实上，存在两个总体结构，即miRNA家族和miRNA簇，本文将结合最新文献以及之前一项专注于机械转导的研究对二者进行详细讨论。文献和我们自己的数据均支持一个新的假说，即miRNA簇主要调节机械转导，影响65%的信号通路。总之，基于miRNA簇提出了一种新的、重要的机械转导调节模式。这一发现为机械转导和动脉粥样硬化的治疗开辟了新途径。
