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
Cell proliferation, RNA processing, RNA binding
Comment
granulosa123
Cellular localization
Cytoplasmic
Comment
others123//////Plasma Levels of miR-27a, miR-130b, and miR-301a in Polycystic Ovary Syndrome. Pourteymour Fard Tabrizi Z et al. (2020) Polycystic ovary syndrome (PCOS) is a gynecological endocrine disorder in women of reproductive age. There is adequate evidence that suggests several microRNAs (miRNAs) are of great importance for PCOS. It seems that dysregulated expression of miR-27a, miR-130b, and miR-301a are associated with PCOS. The aim of this study was to investigate whether plasma levels of these miRNAs are different between patients with PCOS and healthy controls. Fifty-three women with a definite diagnosis of PCOS, and 53 healthy controls were enrolled. MiRNAs expression levels in plasma were evaluated by real-time PCR. The diagnostic values of each miRNA were calculated by the receiver operating characteristic (ROC) curve and areas under the curves (AUC). The main clinical characteristics were not significantly different between the two groups. The circulating plasma expression levels of miR-27a and miR-301a had a significant increase (P = 0.0008 and P <0.0001, respectively) but miR-130b expression level decreased in the patient group (P <0.0001). The AUC for miR-27a, miR-130b, and miR-301a were 0.71, 0.77, and 0.66, respectively. A positive exponential was observed for miR-27a and miR-301a in multiple logistic regression. Changes in the plasma expressions of the studied miRNAs are likely to be associated with PCOS phenotypes. MiR-27a has a potential to serve as a diagnostic biomarker of PCOS.//////////////////
Ovarian function
Oocyte maturation, Early embryo development
Comment
MicroRNAs transfected into granulosa cells may regulate oocyte meiotic competence during in vitro maturation of mouse follicles. Kim YJ 2013 et al.
STUDY QUESTION
Do microRNAs (miRNAs) in granulosa cells (GCs) affect oocyte maturation during ovarian follicle development?
SUMMARY ANSWER
Sophisticated regulation by miRNAs in ovarian GCs may improve oocyte maturation efficiency during ovarian follicle development.
WHAT IS KNOWN ALREADY
The meiotic competence of oocytes depends on the follicle's potential to undergo appropriate maturation and is an important factor in infertility therapies such as IVF. The exact function of the GCs during follicular development remains unknown.
STUDY DESIGN, SIZE, DURATION
After in vitro maturation (IVM) and ovulation induction of isolated ovarian pre-antral follicles from 12-day-old female C57BL6 mice (n = 40), miRNA expression in the GCs was compared according to the maturity of the oocyte (metaphase I (MI) versus metaphase II (MII)). The miRNAs, which showed notable different expression, were modulated by transfection during IVM of follicles.
MATERIALS, SETTING, METHODS
miRNA expression and candidate target gene expression in GCs of isolated murine ovarian pre-antral follicles were evaluated by real-time PCR after IVM. miR mimics and -inhibitors for selected miRNAs were transfected into the in vitro-maturated follicles, and ovulation, oocyte maturation and fertilization rates were compared. Candidate target gene expressions in GC were evaluated by quantitative PCR and immunohistochemistry using confocal microscopy.
MAIN RESULTS AND THE ROLE OF CHANCE
The relative expression of mmu-let-7b (0.78 0.10, P = 0.016), mmu-let-7c (0.78 0.12, P = 0.029), mmu-miR-27a (0.57 0.18, P = 0.016) and mmu-miR-322 (0.59 0.14, P = 0.008) was significantly lower in the GCs of follicles containing MII oocytes compared with those of MI oocytes. Transfection with a mmu-miR-27a-mimic sequence decreased the oocyte maturation rate compared with that for the control (9.4 versus 18.9%, P = 0.042), and transfection with mmu-let-7c-, mmu-miR-27a- and mmu-miR-322-inhibitor sequences increased the oocyte maturation rate by 1.5- to 2.0-folds compared with that for the control (40.6, 31.6, and 30.5%versus 18.9%, P < 0.001, P = 0.013, P = 0.021, respectively). The expression of IGFBP-2 was higher in GCs of MII than in the GCs of MI, and higher in miR-inhibitor transfection groups than in miR-mimic transfection groups and controls.
LIMITATIONS, REASONS FOR CAUTION
An in vitro model was used in lieu of an in vivo model because of the ease of performing miRNA transfection in cell culture. However, studies have shown similarities and differences in in vivo versus in vitro cultured follicles. The findings of the present study need to be confirmed using in vivo maturation models and extended to evaluate developmental competence.
WIDER IMPLICATIONS OF THE FINDINGS
Our findings suggest that sophisticated miRNA regulation in GCs may improve oocyte maturation efficiency during ovarian follicle development.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A111539). None of the authors has any conflicts of interest to declare.
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Expression regulated by
Comment
LncRNA HCP5 promotes cell proliferation and inhibits apoptosis via miR-27a-3p/IGF-1 axis in human granulosa-like tumor cell line KGN. Chen Y et al. (2019) This study aimed to reveal the potential roles of long non-coding RNA HCP5 (lncRNA HCP5) and its potential molecular mechanism in polycystic ovarian syndrome (PCOS). The human granulosa-like tumor cell line KGN was used for assessing the effects of HCP5 in the proliferation and apoptosis of granulosa cells (GCs). The results showed that downregulation of HCP5 suppressed cell proliferation through arresting cell cycle progression at G1 phase, and induced the apoptosis via activating mitochondrial pathway, while overexpression of HCP5 played the opposite effects in KGN cells. We predicted and confirmed miR-27a-3p was a directly target to HCP5 and it could directly bind with insulin-like growth factor-1 (IGF-1). Next, we performed gain- and loss-of-functions approaches by transfecting miR-27a-3p inhibitor into HCP5 knocking down cells and transfecting miR-27a-3p mimics into HCP5 overexpressing cells. The results demonstrated that downregulation and upregulation of miR-27a-3p could block the effects on the proliferation and apoptosis mediated by silencing and overexpressing HCP5 in KGN cells. Additionally, miR-27a-3p inhibitor remarkably reversed the IGF-1 decrease regulated by knocking down HCP5 and miR-27a-3p mimics inhibited the IGF-1 increase modulated by overexpressing HCP5 in KGN cells. Furthermore, we observed that the promoted cell vitality and reduced apoptosis mediated by enforced expression of HCP5 could be alleviated when the KGN cells transfected with IGF-1 siRNA. Our findings indicate that HCP5 might be a potential regulatory factor for development of PCOS through regulating the miR-27a-3p/IGF-1 axis.//////////////////
Ovarian localization
Oocyte, Granulosa
Comment
MicroRNA-27a activity is not suppressed in porcine oocytes. Chen L et al. MicroRNAs (miRNAs) are a class of small noncoding RNAs involved in multiple cellular processes. Recent findings indicate that miRNA activity is globally suppressed in mouse oocytes. However, whether miRNAs are expressed and function in porcine oocytes remains unknown. In this study, our aims were to ascertain if miRNA biogenesis occurs and whether miRNA activity is globally suppressed during porcine oocyte maturation. First, to identify if miRNA biogenesis occurred, a TaqMan low-density array containing 365 mature human miRNAs was used to examine miRNA expression. This analysis revealed dynamic changes in miRNA expression, suggesting miRNA biogenesis during porcine oocyte maturation. Then, to identify if miRNA activity was globally suppressed in porcine oocytes, we focused on miR-27a, which functions in the cell cycle. miR-27a was found to facilitate the first cleavage and repress the translation of its messenger RNA target (MAP2K4), suggesting that miR-27a activity was not suppressed in porcine oocytes. Taken together, our results suggest that miRNA activity was not globally suppressed in porcine oocytes, at least for miR-27a. However, because we only investigated the activity of miR-27a, further experiments are definitely required to ascertain this point.
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Role of microRNAs in premature ovarian insufficiency. Guo Y et al. (2017) Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea lasting for a minimum of 4 months. The typical characteristics comprised of declined estrogen and raised serum concentrations of follicle-stimulating hormone (FSH) in women <40-year-old, primarily originating from iatrogenic factors, karyotypic abnormalities, and genetic factors. However, the etiology of POI remains unknown in approximately 90% of cases. POI could lead to infertility, osteoporosis, cardiovascular disorder, and cognitive dysfunction. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (ncRNAs) that can mediate post-translational silencing of the genes involved in the regulation of proliferation, differentiation, apoptosis, development, tumorigenesis, and hematopoiesis. Recently, the regulatory functions of miRNAs in the development of POI have been the topic of intensive research. The present review addresses the association of miRNAs' machinery genes (Dicer, Drosha, and XPO5) with POI and the miRNA expression profiles in the plasma of patients with POI. In addition, several specific miRNAs (miR-23a, miR-27a, miR-22-3p, miR-146a, miR-196a, miR-290-295, miR-423, and miR-608) related to POI are also examined in order to highlight the issues that deserve further investigation. A thorough understanding of the exact regulatory roles of miRNAs is imperative to gain novel insights into the etiology of idiopathic POI and offer new research directions in the field.//////////////////
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Functional characterization of microRNA-27a-3p expression in human polycystic ovary syndrome. Wang M et al. (2017) The goal of this study was to characterize the function of microRNA-27a-3p (miR-27a-3p) in polycystic ovary syndrome (PCOS). MiR-27a-3p expression was analyzed in excised granulosa cells (GCs) from 21 PCOS and 12 normal patients undergoing IVF cycle treatments, and in 17 non-treated cuneiform ovarian resection PCOS samples and 13 control ovarian samples-from non-PCOS patients. We found that the expression of miR-27a-3p was significantly increased in both excised GCs and the ovaries of PCOS patients compared to the controls. Insulin treatment of the human granulosa-like tumor cell line KGN resulted in decreased downregulated the expression of miR-27a-3p, and this effect appeared to be mediated by STAT1 and STAT3. The overexpression of miR-27a-3p in KGN cells inhibited SMAD5, which in turn decreased cell proliferation and promoted cell apoptosis. After KGN cells were stimulated with insulin for 48 h, there was increased expression of SMAD5 protein and decreased apoptosis. Additionally, knockdown/overexpression of SMAD5 in KGN cells reduced/increased cell number and promoted/ inhibited cell apoptosis. Insulin-stimulated primary GCs isolated from PCOS patients, in contrast to normal GCs or KGN cells, did not exhibit decreased miR-27a-3p expression. The differences in the expression levels in KGN cells and human PCOS GCs are likely explained by increased miR-27a-3p expression in the GCs caused by insulin resistance in PCOS. Taken together, our data provided evidence for a functional role of miR-27a-3p in the GCs dysfunction that occurs in human PCOS patients.//////////////////