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. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
General function
RNA metabolism
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Cellular localization
Cytoplasmic
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Ovarian function
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miR-483-5p and miR-486-5p are down-regulated in cumulus cells of metaphase II oocytes from women with polycystic ovary syndrome. Shi L et al. (2015) The aim of this study was to compare the expression of microRNAs (miRNAs) in cumulus cells from polycystic ovary syndrome (PCOS) and non-PCOS women. In the present study, miRNA expression profiles of the cumulus cell samples were determined by miRNA microarrays. Quantification of selected miRNAs and predicted target genes was performed using quantitative real-time PCR (qRT-PCR). The results showed that miR-483-5p and miR-486-5p are significantly decreased in cumulus cells of PCOS patients PCOS (fold change >2, false discovery rate <0.001). qRT-PCR found that four predicted genes, SOCS3, SRF, PTEN and FOXO1, were significantly increased in PCOS cumulus cells (all P < 0.001), and IGF2 (host gene of miR-483-5p) was significantly decreased in PCOS cumulus cells (P < 0.001). These results indicated that miR-483-5p might play an important role in reducing insulin resistance, and that miR-486-5p might promote cumulus cell proliferation through activation of PI3K/Akt. The findings from this study provided new insights into the complex molecular mechanisms involved in PCOS by revealing pathways possibly regulated by miRNAs. The differences in miRNAs (miR-483-5p, miR-486-5p) and their target gene expression in cumulus cells may provide clues for future research and help to explain aberrant follicular development and subfertility in women with PCOS.//////////////////
Characterization of microRNA profile in human cumulus granulosa cells: identification of microRNAs that regulate Notch signaling and are associated with PCOS. Xu B et al. (2015) Polycystic ovary syndrome (PCOS), a complex and heterogeneous endocrine condition, is characterized by polycystic ovaries, hyperandrogenism, insulin resistance and chronic anovulation. Cumulus granulosa cells surrounding the oocyte are involved in different aspects of PCOS pathology. Several studies suggested that miRNAs play an important regulatory role at the post-transcriptional level in cumulus granulosa cells. Our objective was to describe the altered miRNA expression profiles and miRNA targeted signaling pathways in PCOS. Case-control study that involved 21 women with PCOS and 20 women without the disease (controls).The miRNA expression profiles of human cumulus granulosa cells were determined using next generation sequencing by Illumina Hiseq 2000. The differentially expressed miRNAs and novel miRNAs were validated by quantitative real-time PCR. The Notch3 and MAPK3 were demonstrated to be targeted by miR-483-5p based on quantitative real-time PCR, western blot and luciferase activity assay. Compared to controls, a total of 59 known miRNA were identified that differentially expressed in PCOS cumulus granulosa cells, including 21 miRNAs increase and 38 miRNAs decrease. Moreover, the novel miRNAs were predicted in PCOS and control cumulus granulosa cells. The potential regulating roles of miRNA in pathophysiology of PCOS were analyzed by GO and KEGG pathway annotation, and several important processes were identified to be targeted by the differentially expressed miRNAs, such as Notch signaling, regulation of hormone, and energy metabolism. Furthermore, Notch3 and MAPK3, the members of Notch signalling and ERK-MAPK pathway, were demonstrated to be regulated by miR-483-5p based on negative expression correlation validation and detection of Notch3/MAPK3 expression after miR-483-5p mimics transfection. Dual luciferase activity assay suggested that Notch3 and MAPK3 were directly targeted by miR-483-5p. Our data suggested that miRNAs and their targeted pathways (e.g. Notch signaling pathway) play important roles in the etiology and pathophysiology of PCOS, and provides novel candidates for molecular biomarkers or treatment targets in the research of female infertility associated to PCOS.//////////////////
Expression regulated by
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Ovarian localization
Cumulus, Granulosa
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miR-483 is Down-Regulated in Polycystic Ovarian Syndrome and Inhibits KGN Cell Proliferation via Targeting Insulin-Like Growth Factor 1 (IGF1). Xiang Y et al. (2016) BACKGROUND Polycystic ovarian syndrome (PCOS) is a common metabolic disorder in premenopausal woman, characterized by hyperandrogenism, oligoanovulation, and insulin resistance. microRNAs play pivotal roles in regulating key factors of PCOS. However, relevant research remains limited. This study aimed to reveal the role and potential mechanism of miR-483 in PCOS. MATERIAL AND METHODS PCOS patients (n=20) were recruited for detecting miR-483 expression in lesion and normal ovary cortex. Human granulosa-like tumor cell line KGN was used to alter miR-483 expression by cell transfection. Cell viability and proliferation were analyzed by MTT assay and colony formation assay, and cell cycle was detected by flow cytometry. Interaction between miR-483 and IGF1 was verified by luciferase reporter assay. KGN cells were further treated by insulin to investigate the relationship between miR-483 and insulin. RESULTS miR-483 was significantly down-regulated in lesion ovary cortex from PCOS patients (P<0.001). In KGN cells, overexpression of miR-483 inhibited cell viability and proliferation, and induced cell cycle arrest. miR-483 also inhibited CCNB1, CCND1, and CDK2. miR-483 sponge induced the opposite effects. miR-483 directly targeted IGF1 3'UTR, and IGF1 promoted KGN cell proliferation and reversed miR-483-inhibited cell viability. Insulin treatment in KGN cells inhibited miR-483, and promoted IGF1 and cell proliferation. CONCLUSIONS These results suggest that miR-483 is a PCOS suppressor inhibiting cell proliferation, possibly via targeting IGF1, and that it is involved in insulin-induced cell proliferation. miR-483 is a potential alternative for diagnosing and treating PCOS.//////////////////