Concise Review: New Frontiers in MicroRNA-Based Tissue Regeneration

Frith, Jessica E.; Porrello, Enzo R.; Cooper-White, Justin J.

doi:10.5966/sctm.2014-0032

Cited by 27 publications

(22 citation statements)

References 81 publications

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“…Through our analysis of previously published small RNA sequencing of ASCs, we determined that miRNAs, such as miR-222 Ã , were expressed as truncated isomiRs with alternative 5 0 ends. As the 5 0 end of the miRNA dictates mRNA target selection, this may account for differences in miRNA/mRNA target selection; however, further studies are necessary [29,30].…”

Section: Discussionmentioning

confidence: 99%

Mirna biogenesis pathway is differentially regulated during adipose derived stromal/stem cell differentiation

et al. 2018

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Stromal/stem cell differentiation is controlled by a vast array of regulatory mechanisms. Included within these are methods of mRNA gene regulation that occur at the level of epigenetic, transcriptional, and/or posttranscriptional modifications. Current studies that evaluate the posttranscriptional regulation of mRNA demonstrate microRNAs (miRNAs) as key mediators of stem cell differentiation through the inhibition of mRNA translation. miRNA expression is enhanced during both adipogenic and osteogenic differentiation; however, the mechanism by which miRNA expression is altered during stem cell differentiation is less understood. Here we demonstrate for the first time that adipose-derived stromal/stem cells (ASCs) induced to an adipogenic or osteogenic lineage have differences in strand preference (-3p and -5p) for miRNAs originating from the same primary transcript. Furthermore, evaluation of miRNA expression in ASCs demonstrates alterations in both miRNA strand preference and 5'seed site heterogeneity. Additionally, we show that during stem cell differentiation there are alterations in expression of genes associated with the miRNA biogenesis pathway. Quantitative RT-PCR demonstrated changes in the Argonautes (AGO1-4), Drosha, and Dicer at intervals of ASC adipogenic and osteogenic differentiation compared to untreated ASCs. Specifically, we demonstrated altered expression of the AGOs occurring during both adipogenesis and osteogenesis, with osteogenesis increasing AGO1-4 expression and adipogenesis decreasing AGO1 gene and protein expression. These data demonstrate changes to components of the miRNA biogenesis pathway during stromal/stem cell differentiation. Identifying regulatory mechanisms for miRNA processing during ASC differentiation may lead to novel mechanisms for the manipulation of lineage differentiation of the ASC through the global regulation of miRNA as opposed to singular regulatory mechanisms.

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Section: Discussionmentioning

confidence: 99%

Mirna biogenesis pathway is differentially regulated during adipose derived stromal/stem cell differentiation

et al. 2018

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“…Therefore, the delivery of synthetic small RNAs [small interfering (si)RNA and micro (mi) RNAs] plays a vital role as a trigger of the RNAi mechanism. It allows finely modulated target gene expression and hence regulates protein expression of the target tissue (3). This finding has great therapeutic potential for numerous diseases and injuries by enhancing regeneration capacity (4, 5).…”

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confidence: 99%

“…This finding has great therapeutic potential for numerous diseases and injuries by enhancing regeneration capacity (4, 5). Several small‐RNA delivery methods have been applied recently to the treatment of genetic diseases and cancers (6, 7), but thus far, few applications have been attempted that involve tissue engineering and regenerative medicine strategies to repair traumatic injury (3, 8, 9).…”

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confidence: 99%

Combination of small RNAs for skeletal muscle regeneration

et al. 2015

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Selectively controlling the expression of the target genes through RNA interference (RNAi) has significant therapeutic potential for injuries or diseases of tissues. We used this strategy to accelerate and enhance skeletal muscle regeneration for the treatment of muscular atrophy. In this study, we used myostatin small interfering (si)RNA (siGDF-8), a major inhibitory factor in the development and postnatal regeneration of skeletal muscle and muscle-specific microRNAs (miR-1 and -206) to further accelerate muscle regeneration. This combination of 3 small RNAs significantly improved the gene expression of myogenic regulatory factors in vitro, suggesting myogenic activation. Moreover, cell proliferation and myotube formation improved without compromising each other, which indicates the myogenic potential of this combination of small RNAs. The recovery of chemically injured tibialis anterior muscles in rats was significantly accelerated, both functionally and structurally. This novel combination of siRNA and miRNAs has promising therapeutic potential to improve in situ skeletal muscle regeneration.-Kim, N., Yoo, J. J., Atala, A., Lee, S. J. Combination of small RNAs for skeletal muscle regeneration. FASEB J. 30, 1198-1206 (2016). www.fasebj.org

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“…What fills part of this void is the emergent observations that span the diverse phylogenetic tree of the animal kingdom, demonstrating that miRNAs play a key role in tissue repair and regeneration. 29 Given their capacity to determine the functional fate of coding genes and therefore a large network of downstream signaling pathways, 30 miRNAs are rapidly emerging as potential candidates for the therapeutic modulation of tissue repair and regeneration. In this context, it is of extraordinary importance that the turnover of miRNA within the cell determines its functional fate.…”

Section: Development Is the Key To Regenerationmentioning

confidence: 99%