Let-7 as a Promising Target in Aging and Aging-Related Diseases: A Promise or a Pledge

Abstract

The abnormal regulation and expression of microRNA (miRNA) are closely related to the aging process and the occurrence and development of aging-related diseases. Lethal-7 (let-7) was discovered in Caenorhabditis elegans (C. elegans) and plays an important role in development by regulating cell fate regulators. Accumulating evidence has shown that let-7 is elevated in aging tissues and participates in multiple pathways that regulate the aging process, including affecting tissue stem cell function, body metabolism, and various aging-related diseases (ARDs). Moreover, recent studies have found that let-7 plays an important role in the senescence of B cells, suggesting that let-7 may also participate in the aging process by regulating immune function. Therefore, these studies show the diversity and complexity of let-7 expression and regulatory functions during aging. In this review, we provide a detailed overview of let-7 expression regulation as well as its role in different tissue aging and aging-related diseases, which may provide new ideas for enriching the complex expression regulation mechanism and pathobiological function of let-7 in aging and related diseases and ultimately provide help for the development of new therapeutic strategies.

Integration of Transcriptome and MicroRNA Profile Analysis of iMSCs Defines Their Rejuvenated State and Conveys Them into a Novel Resource for Cell Therapy in Osteoarthritis

“…Specifically, the down-regulated hsa-let-7 in iMSCs, which has been shown to exhibit crucial effects on MSCs regenerative properties, showed reduced expression after iPSCs reprogramming, and this reduction was also observed during iMSCs differentiation [ 79 , 80 ]. In concordance, previous studies have shown that hsa-let7b/i is elevated in aging tissues and participates in multiple pathways regulating the aging process, negatively affecting tissue stem cell function [ 81 ].…”

Genetically engineered M2-like macrophage-derived exosomes for P. gingivalis-suppressed cementum regeneration: From mechanism to therapy

“…The membrane structure of exosomes prevents the RNA contained in exosomes from being degraded, thus playing a more stable role. Let-7 miRNAs were the first discovered human miRNA with highly conserved sequence and function between species [ 30 ], and were revealed to be involved in different biological processes, including osteogenesis [ [31] , [32] , [33] , [34] ]. Related studies have found that Let-7 miRNAs were closely related to M2 macrophage polarization [ 35 , 36 ].…”

MiRNA-Based Therapies for Lung Cancer: Opportunities and Challenges?

“…MiRNA replacement therapy is based on delivering exogenous miRNAs to patients to regulate abnormal functions [ 21 ]. For instance, let-7 is highly expressed in normal lung tissue and downregulated in lung cancer cells [ 23 ]. Let-7a inhibits NIRF expression in lung cancer while increasing p21 WAF1 expression and inhibiting cell proliferation [ 24 ].…”