miR-206 Mediates YAP-Induced Cardiac Hypertrophy and Survival. Yang Y et al. (2015) In Drosophila, the Hippo signaling pathway negatively regulates organ size by suppressing cell proliferation and survival through the inhibition of Yorkie, a transcriptional co-factor. Yes-associated protein (YAP), the mammalian homolog of Yorkie, promotes cardiomyocyte growth and survival in postnatal hearts. However, the underlying mechanism responsible for the beneficial effect of YAP in cardiomyocytes remains unclear. We investigated whether miR-206, a microRNA known to promote hypertrophy in skeletal muscle, mediates the effect of YAP upon promotion of survival and hypertrophy in cardiomyocytes. Microarray analysis indicated that YAP increased miR-206 expression in cardiomyocytes. Increased miR-206 expression induced cardiac hypertrophy and inhibited cell death in cultured cardiomyocytes, similar to that of YAP. Down regulation of endogenous miR-206 in cardiomyocytes attenuated YAP-induced cardiac hypertrophy and survival, suggesting that miR-206 plays a critical role in mediating YAP function. Cardiac-specific overexpression of miR-206 in mice induced hypertrophy and protected the heart from ischemia/reperfusion (I/R) injury, whereas suppression of miR-206 exacerbated I/R injury and prevented pressure overload-induced cardiac hypertrophy. miR-206 negatively regulates FoxP1 expression in cardiomyocytes and overexpression of FoxP1 attenuated miR-206-induced cardiac hypertrophy and survival, suggesting that FoxP1 is a functional target of miR-206. YAP increases the abundance of miR-206, which in turn plays an essential role in mediating hypertrophy and survival by silencing FoxP1 in cardiomyocytes.//////////////////
NCBI Summary:
microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. Disruption of the encoded miRNA has been implicated in multiple skeletal muscle disorders, including amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD), as well as in several cancers. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Aug 2017]
General function
RNA metabolism, RNA processing
Comment
Cellular localization
Cytoplasmic
Comment
miR-206 serves an important role in polycystic ovary syndrome through modulating ovarian granulosa cell proliferation and apoptosis. Zhou J et al. (2021) An increasing number of studies have reported that microRNAs (miRNAs) have an important role in polycystic ovary syndrome (PCOS). Downregulation of miR-206 in patients with PCOS has been found, however, its specific role remains unclear. The present study aimed to investigate the roles of miR-206 in (PCOS) and to determine the underlying molecular mechanisms. Reverse transcription-quantitative PCR (RT-qPCR) was performed to analyze the expression levels of miR-206 in normal ovarian surface epithelial IOSE80 cells and human ovarian granulosa cell-like KGN cells. TargetScan was used to predict the target gene of miR-206, which was subsequently verified using a dual-luciferase reporter gene assay. The mRNA expression levels of cyclin D2 (CCND2) and the transfection efficiencies of the miR-206 mimic and CCDN2 overexpression plasmid were determined using RT-qPCR analysis. The protein expression levels of CCND2, cleaved-caspase-3 and pro-caspase-3 were analyzed using western blotting, and an MTT assay and flow cytometric analysis were used to evaluate the cell viability and levels of apoptosis, respectively, in the cells following transfection. Finally, the activity of caspase-3 was analyzed using a caspase-3 activity assay kit. The results of the present study revealed that the expression levels of miR-206 were downregulated in KGN cells compared with IOSE80 cells. CCND2 was predicted and verified to be a direct target gene of miR-206, and the mRNA and protein expression levels of CCND2 were discovered to be upregulated in KGN cells compared with IOSE80 cells. The miR-206 mimic and CCND2 overexpression plasmid significantly upregulated the expression levels of miR-206 and CCND2, respectively, in KGN cells. The miR-206 mimic also downregulated the expression levels of CCND2 in KGN cells, while this effect was reversed following the transfection with the CCND2 overexpression plasmid. Compared with the mimic control group, the miR-206 mimic significantly decreased the cell viability, induced the levels of apoptosis, increased the activity of caspase-3, upregulated cleaved-caspase-3 protein expression levels and downregulated pro-caspase-3 protein expression levels in KGN cells following transfection; these effects were reversed following the overexpression of CCND2. In conclusion, the findings of the present study suggested that miR-206 may serve an important role in PCOS through modulating ovarian granulosa cell viability and apoptosis.//////////////////