Biogenesis, evolution and functional targets of microRNA-125a

Abstract

MicroRNAs are small non-coding RNAs that regulate gene expression at post-transcriptional level by inhibiting translation of complementary mRNAs and/or targeting them for degradation. MicroRNAs play crucial roles in development, cell differentiation, and apoptosis. In addition, recent studies indicate that they are important regulators of virus-host interactions. MicroRNA-125a is a homolog of C. elegans lin-4, the first discovered microRNA, shown to dictate the onset of larval stages in the nematode. In this review, we focus on the gene structure of microRNA-125a, its evolution, its expression pattern in mammalian organs and tissues, and its functional targets. Overall, the available data indicate that microRNA-125a plays crucial roles both in development and in the adult tissues. In fact, it (1) contributes to the control of phase transitions in development and/or cell differentiation; (2) regulates the expression of several target proteins that are involved in cell proliferation, apoptosis, and migration; (3) interferes with the expression of the hepatitis B virus surface antigen in liver cells, thus counteracting viral replication. These findings suggest that delivery of microRNA-125a mimics or treatments that modulate its cellular expression may be valuable tools for the development of new therapeutic strategies for human diseases, including cancer and viral hepatitis B.

Targeted Delivery of MicroRNA125a-5p by Engineered Lipid Nanoparticles for the Treatment of HER2 Positive Metastatic Breast Cancer

“…22 This work was supported through biopsy sample acquisition and consequent analysis of the breast tissue to validate knockdown of miR125a and miR125b in HER2 amplified and HER2 overexpressing breast cancers. [23][24][25] Despite the salient features of miRNAs, the development of therapeutics is currently limited due to their instability in circulation, lack of active targeting to specific cell populations, potential for unwanted stimulation of an immune response, and inability to traverse the phospholipid bilayer of cell membranes. There is a critical need to develop drug delivery platforms in order to expedite the clinical translation of miRNA based therapeutics.…”

MicroRNA-125a-5p induces mouse granulosa cell apoptosis by targeting signal transducer and activator of transcription 3

“…A recent study indicated that miR-125a-5p can control phase transitions in cell differentiation and growth by regulating target genes involved in cell proliferation, apoptosis, and migration. 35 Interestingly, we observed an inverse relationship between expression of miR-125a-5p and expression of STAT3 in CP-treated mGCs. Based on these findings, we hypothesized that miR-125a-5p promoted mGC apoptosis by targeting the STAT3 gene.…”

“…35 In ERBB2-overexpressing breast cancer cells and ovarian carcinoma cells, miR-125a-5p was down-regulated and stimulated apoptosis. 10,15 On the other hand, miR-125a-5p antagonism led to induction of multiple myeloma cell apoptosis by regulation of the p53 gene.…”

Plasma MicroRNAs Relate to Atrial Fibrillation Recurrence after Catheter Ablation: Longitudinal Findings from the MiRhythm Study

“…These targets include ERBB2/3 (receptor tyrosine kinase of EGF receptor family), HuR (RNA-binding protein), and MMP11/12 (matrix metalloproteinases), as well as p53 (key tumor suppressor gene), Bak1 (pro-apoptotic protein), and TNFAIP3 (negative regulator of NF-kB signaling pathway; Table 3) [20][21][22][23]. miR-125a inhibits MMP11/12 activity and thus higher cardiac miR-125a expression is likely associated with greater fibrosis and extracellular collagen deposition.…”

“…We further hypothesized that the identified miRNAs would have mechanistic associations with electrostructural cardiac remodeling. To test these hypotheses, we quantified pre-ablation plasma expression of 86 miRNAs in 83 participants and repeated profiling 1-month post-ablation in a subset of 43 participants in a prospectively recruited, contemporary cohort with AF referred for CA and then examined associations between miRNA expressions with AF recurrence over 12 months [17][18][19][20][21][22][23][24][25].…”