MicroRNAs and ovarian function
TL;DR: The current understanding of miRNA biogenesis, the role and mechanism that miRNAs play in post-transcriptional gene expression regulation, and specifically the current evidence of mi RNA involvement in ovarian development and function are reviewed.
Abstract: MicroRNAs (miRNAs) are a class of small non-coding RNAs which function in gene regulation with an important role in cell proliferation, maturation, and activity. The regulatory role of these small RNA molecules has recently begun to be explored in ovarian cells, uncovering their influence on gonadal development, steroidogenesis, apoptosis, ovulation, and corpus luteum development. This emerging area of research has extended and reshaped our understanding on how ovarian function is regulated. Here, we review the current understanding of miRNA biogenesis, the role and mechanism that miRNAs play in post-transcriptional gene expression regulation, and specifically the current evidence of miRNA involvement in ovarian development and function. Future comprehensive understanding of the role of miRNAs in the ovary in both physiological and pathological conditions may offer new treatment strategies for infertility and other ovarian disorders.
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TL;DR: The present data indicates that miR-92b directly regulate cell proliferation and apoptosis by targeting DKK3 and act as prognostic factors for glioma patients.
Abstract: MiR-92b was upregulated in gliomas. However, the association of miR-92b with glioma cell apoptosis and survival remains unknown. Proliferation capability of glioma cells upon tranfection with miR-92b mimics or inhibitors was detected by mutiple analyses, including MTT assays, colony formation assay. Apoptosis abilities of glioma cells were detected by flow cytometric analysis. The target of miR-92b was determined by luciferase reporter and western blot. The association of miR-92b with outcome was examined in twenty glioma patients. MiR-92b expression was significantly increased in high-grade gliomas compared with low-grade gliomas, and positively correlated with the degree of glioma infiltration. Over-expression of miR-92b increased cell proliferation, whereas knockdown of miR-92b decreased cell proliferation via modulating the levels of the target, Target prediction analysis and a dual luciferase reporting assay confirmed that the inhibitory protein-coding Dickkopf-3 gene (DKK3) was a direct target of miR-92b. Furthermore, miR-92b could regulate the expression of downstream genes of the Wnt/beta-catenin signaling pathway, such as Bcl2, c-myc and p-c-Jun, in glioma cells. Finally, the increased level of miR-92b expression in high-grade gliomas confers poorer overall survival. The present data indicates that miR-92b directly regulate cell proliferation and apoptosis by targeting DKK3 and act as prognostic factors for glioma patients.
45 citations
TL;DR: The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women.
Abstract: Obese women exhibit decreased fertility, high miscarriage rates and dysfunctional corpus luteum (CL), but molecular mechanisms are poorly defined. We hypothesized that weight gain induces alterations in CL gene expression. RNA sequencing was used to identify changes in the CL transcriptome in the vervet monkey (Chlorocebus aethiops) during weight gain. 10 months of high-fat, high-fructose diet (HFHF) resulted in a 20% weight gain for HFHF animals vs. 2% for controls (p = 0.03) and a 66% increase in percent fat mass for HFHF group. Ovulation was confirmed at baseline and after intervention in all animals. CL were collected on luteal day 7–9 based on follicular phase estradiol peak. 432 mRNAs and 9 miRNAs were differentially expressed in response to HFHF diet. Specifically, miR-28, miR-26, and let-7b previously shown to inhibit sex steroid production in human granulosa cells, were up-regulated. Using integrated miRNA and gene expression analysis, we demonstrated changes in 52 coordinately regulated mRNA targets corresponding to opposite changes in miRNA. Specifically, 2 targets of miR-28 and 10 targets of miR-26 were down-regulated, including genes linked to follicular development, steroidogenesis, granulosa cell proliferation and survival. To the best of our knowledge, this is the first report of dietary-induced responses of the ovulating ovary to developing adiposity. The observed HFHF diet-induced changes were consistent with development of a dysfunctional CL and provide new mechanistic insights for decreased sex steroid production characteristic of obese women. MiRNAs may represent novel biomarkers of obesity-related subfertility and potential new avenues for therapeutic intervention.
43 citations
Cites background from "MicroRNAs and ovarian function"
...Specifically, Let-7b and miR -28 have been shown to inhibit progesterone and testosterone production in human granulosa cells (GC), while miR26a and miR-28 suppress estrogen secretion [44–46]....
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TL;DR: This study provides the first evidence for post-transcriptional regulation of PGR and further elucidates the role of miR-378-3p in the ovary.
42 citations
TL;DR: It is shown that miR-1275 promotes early apoptosis of porcine granulosa cells (pGCs) and the initiation of follicular atresia, and inhibits E2 release and expression of CYP19A1, the key gene in E2 production.
39 citations
TL;DR: Target analysis of the differentially expressed miRNA resulted in genes involved in regulating apoptosis and immune response, providing evidence that miRNAs regulate the intracellular pathways that lead to either luteal regression or survival.
39 citations
Cites background from "MicroRNAs and ovarian function"
...Several studies have demonstrated a role of specific miRNA in cells frommale and female reproductive tissues, as reviewed by Baley and Li (2012), Donadeu et al....
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References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
32,946 citations
"MicroRNAs and ovarian function" refers background in this paper
...The genes that encode miRNAs, which comprise a class of naturally occurring, small non-coding RNAs, are generally transcribed by RNA polymerase II, processed into short hairpin RNAs by the enzyme Drosha and its RNA-binding cofactor DiGeorge syndrome critical region gene 8 (DGCR8), as shown in Figure 1 [4-7]....
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TL;DR: To their surprise, it was found that double-stranded RNA was substantially more effective at producing interference than was either strand individually, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process.
Abstract: Experimental introduction of RNA into cells can be used in certain biological systems to interfere with the function of an endogenous gene Such effects have been proposed to result from a simple antisense mechanism that depends on hybridization between the injected RNA and endogenous messenger RNA transcripts RNA interference has been used in the nematode Caenorhabditis elegans to manipulate gene expression Here we investigate the requirements for structure and delivery of the interfering RNA To our surprise, we found that double-stranded RNA was substantially more effective at producing interference than was either strand individually After injection into adult animals, purified single strands had at most a modest effect, whereas double-stranded mixtures caused potent and specific interference The effects of this interference were evident in both the injected animals and their progeny Only a few molecules of injected double-stranded RNA were required per affected cell, arguing against stochiometric interference with endogenous mRNA and suggesting that there could be a catalytic or amplification component in the interference process
15,374 citations
"MicroRNAs and ovarian function" refers background in this paper
...MicroRNAs (miRNAs) are small (19-25 bp) RNAs that diversely regulate gene expression through their decrease of messenger RNA (mRNA) stability or translation [1-3]....
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TL;DR: In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of the gene set.
11,624 citations
"MicroRNAs and ovarian function" refers background in this paper
...It has been estimated that 30-90% of messenger RNAs may be subjected to miRNA regulation, and individual miRNAs are predicted to target up to several hundred genes [14-16]....
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TL;DR: The results indicate that miRNAs are extensively involved in cancer pathogenesis of solid tumors and support their function as either dominant or recessive cancer genes.
Abstract: Small noncoding microRNAs (miRNAs) can contribute to cancer development and progression and are differentially expressed in normal tissues and cancers From a large-scale miRnome analysis on 540 samples including lung, breast, stomach, prostate, colon, and pancreatic tumors, we identified a solid cancer miRNA signature composed by a large portion of overexpressed miRNAs Among these miRNAs are some with well characterized cancer association, such as miR-17-5p, miR-20a, miR-21, miR-92, miR-106a, and miR-155 The predicted targets for the differentially expressed miRNAs are significantly enriched for protein-coding tumor suppressors and oncogenes (P < 00001) A number of the predicted targets, including the tumor suppressors RB1 (Retinoblastoma 1) and TGFBR2 (transforming growth factor, beta receptor II) genes were confirmed experimentally Our results indicate that miRNAs are extensively involved in cancer pathogenesis of solid tumors and support their function as either dominant or recessive cancer genes
5,791 citations
"MicroRNAs and ovarian function" refers background in this paper
...In addition, miRNAs may also increase translation of specific mRNAs in a manner dependent on the cell cycle [25], and a large number of miRNAs may be expressed in a tissue-specific manner [26]....
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TL;DR: This work has revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access, which has direct implications for fundamental biology as well as disease etiology and treatment.
4,490 citations
"MicroRNAs and ovarian function" refers background in this paper
...Recognition is thought to mainly involve base pairing of miRNA nucleotides 2-8, representing the seed sequence [13]....
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