MicroRNA regulation of BAG3

B-cell lymphoma 2 (Bcl-2)-associated athanogene 3 (BAG3) protein is a member of BAG family of co-chaperones that modulates major biological processes, including apoptosis, autophagy, and development to promote cellular adaptive responses to stress stimuli. Although BAG3 is constitutively expressed in several cell types, its expression is also inducible and is regulated by microRNAs (miRNAs). miRNAs are small non-coding RNAs that mostly bind to the 3′-UTR (untranslated region) of mRNAs to inhibit their translation or to promote their degradation. miRNAs can potentially regulate over 50% of the protein-coding genes in a cell and therefore are involved in the regulation of all major functions, including cell differentiation, growth, proliferation, apoptosis, and autophagy. Dysregulation of miRNA expression is associated with pathogenesis of numerous diseases, including peripheral artery disease (PAD). BAG3 plays a critical role in regulating the response of skeletal muscle cells to ischemia by its ability to regulate autophagy. However, the biological role of miRNAs in the regulation of BAG3 in biological processes has only been elucidated recently. In this review, we discuss how miRNA may play a key role in regulating BAG3 expression under normal and pathological conditions.

Explore synergistic and competitive miRNA regulation mechanisms in the miRNA-mRNA regulatory network from the information decomposition perspective

Since multiple microRNAs can target 3' untranslated regions of the same mRNA transcript, it is likely that these endogenous microRNAs may form synergistic alliances, or compete for the same mRNA harbouring overlapping binding site matches. Synergistic and competitive microRNA regulation is an intriguing yet poorly elucidated mechanism. We here introduce a computational method based on the multivariate information measurement to quantify such implicit interaction effects between microRNAs. Our informatics method of integrating sequence and expression data is designed to establish the functional correlation between microRNAs. To demonstrate our method, we exploited TargetScan and The Cancer Genome Atlas data. As a result, we indeed observed that the microRNA pair with neighbouring binding site(s) on the mRNA is likely to trigger synergistic events, while the microRNA pair with overlapping binding site(s) on the mRNA is likely to cause competitive events, provided that the pair of microRNAs has a high functional similarity and the corresponding triplet presents a positive/negative 'synergy-redundancy' score.

The promise of microRNA-based therapies in Alzheimer’s disease: challenges and perspectives

Multi-pathway approaches for the treatment of complex polygenic disorders are emerging as alternatives to classical monotarget therapies and microRNAs are of particular interest in that regard. MicroRNA research has come a long way from their initial discovery to the cumulative appreciation of their regulatory potential in healthy and diseased brain. However, systematic interrogation of putative therapeutic or toxic effects of microRNAs in (models of) Alzheimer’s disease is currently missing and fundamental research findings are yet to be translated into clinical applications. Here, we review the literature to summarize the knowledge on microRNA regulation in Alzheimer’s pathophysiology and to critically discuss whether and to what extent these increasing insights can be exploited for the development of microRNA-based therapeutics in the clinic.

The Interaction between microRNAs and the Wnt/β-catenin Signaling Pathway in Osteoarthritis

Osteoarthritis (OA) is a chronic disease affecting the whole joint, which still lacks a disease-modifying treatment. This suggests an incomplete understanding of underlying molecular mechanisms. The Wnt/β-catenin pathway is involved in different pathophysiological processes of OA. Interestingly, both excessive stimulation and suppression of this pathway can contribute to the pathogenesis of OA. microRNAs have been shown to regulate different cellular processes in different diseases, including the metabolic activity of chondrocytes and osteocytes. To bridge these findings, here we attempt to give a conclusive overview of microRNA regulation of the Wnt/β-catenin pathway in bone and cartilage, which may provide insights to advance the development of miRNA-based therapeutics for OA treatment.