Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome.
Exosomal circ_0008285 in follicle fluid regulates the lipid metabolism through the miR-4644/ LDLR axis in polycystic ovary syndrome.
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DOI：
10.1186/s13048-023-01199-x
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发表时间：
2023-06-15
影响因子：
4
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中科院分区：
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外泌体环状rna作为卵泡微环境的重要介质，在多囊卵巢综合征（PCOS）的病因学和病理生物学研究中都有涉及。本研究旨在检测PCOS患者卵泡液（FF）外泌体中异常环状RNA （circRNA）的表达谱，并确定circ_0008285/microRNA (miR)-4644/低密度脂蛋白受体（LDLR）轴在PCOS中的作用。67名接受IVF/ICSI的女性，31名PCOS患者和36名非PCOS患者纳入队列研究。通过RNA测序比较PCOS组（n = 3）和对照组（n = 3） FF外泌体的circRNA表达谱。在另一个队列中（PCOS:28 vs Control:33），通过qRT-PCR进一步验证了FF外泌体中四个circRNAs的mRNA表达水平。生物信息学分析和双荧光素酶报告基因测定证实了circ_0008285与miR-4644以及miR-4644与LDLR之间的关系。用sh-circ0008285感染KGN细胞，并用miR-4644 mimic转染，验证其在脂质代谢中的作用。4种circrna的表达有显著差异。Circ_0044234在PCOS患者中过表达，而circ_0006877、circ_0013167和circ0008285在PCOS患者中表达降低。在四个差异表达的circRNAs中，通过GO和KEGG途径分析，circ0008285在脂蛋白颗粒受体活性和胆固醇代谢途径中富集。荧光素酶测定证实了竞争内源性RNA （ceRNA）网络circ_0008285/miR-4644 /LDLR。对circ_0008285的细胞间实验及其在KGN细胞中的减少表明，在外泌体中消耗circ_0008285可以增加受体细胞中miR-4644的表达，抑制LDLR的表达，并增加游离脂肪酸的分泌。Circ_0008285可联合miR-4644促进PCOS卵巢颗粒细胞LDLR的表达，影响卵巢颗粒细胞胆固醇代谢。我们的发现揭示了circ_0008285的ceRNA网络，为研究PCOS的脂质代谢异常提供了新的途径。在线版本包含补充资料，网址为10.1186/s13048-023-01199-x。
Exosomal circRNA, as an essential mediator of the follicular microenvironment, has been implicated in the etiological and pathobiological studies of polycystic ovarian syndrome (PCOS). This study aimed to determine abnormal circular RNA (circRNA) expression profiles in follicle fluid (FF) exosomes in patients with PCOS and identify the role of circ_0008285/microRNA (miR)-4644/low-density lipoprotein receptor (LDLR) axis in PCOS. Sixty-seven women undergoing IVF/ICSI, 31 PCOS patients and 36 non-PCOS patients were included in the cohort study. The circRNA expression profiles of FF exosomes in PCOS (n = 3) and control group (n = 3) were compared by RNA sequencing. In an additional cohort (PCOS:28 vs Control:33), the mRNA expression levels of four circRNAs from FF exosomes were further verified by qRT-PCR. Bioinformatic analysis and dual luciferase reporter gene assay verified the relationship between circ_0008285 and miR-4644 and between miR-4644 and LDLR. KGN cells were infected with sh-circ0008285 and transfected with miR-4644 mimic to verify their roles in lipid metabolism. Four circRNAs showed significantly different expressions. Circ_0044234 was overexpressed in PCOS patients, while circ_0006877, circ_0013167 and circ0008285 were decreased in PCOS. Among four differentially expressed circRNAs, circ0008285 was enriched in lipoprotein particle receptor activity and cholesterol metabolism pathway by GO and KEGG pathway analyses. Luciferase assay confirmed the competing endogenous RNA (ceRNA) network circ_0008285/miR-4644 /LDLR. The intercellular experiments on circ_0008285 and its reduction in KGN cells showed that the consumption of circ_0008285 in exosomes could increase the expression of miR-4644 in recipient cells and inhibit the expression of LDLR, as well as increase free fatty acid secretion. Circ_0008285 can combine with miR-4644 to promote the expression of LDLR and affect the cholesterol metabolism of ovarian granulosa cells in PCOS. Our findings revealed the ceRNA network of circ_0008285 and provided a new path to investigate lipid metabolism abnormalities in PCOS. The online version contains supplementary material available at 10.1186/s13048-023-01199-x.
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DOI：
10.1186/s12958-021-00749-6
发表时间：
2021-05-17
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Yu L;Liu M;Wang Z;Liu T;Liu S;Wang B;Pan B;Dong X;Guo W
通讯作者：
Guo W
低密度脂蛋白受体影响雌性小鼠的生育能力。
影响因子：
1.9
作者：
Guo, Tao;Zhang, Liang;Zhang, Cong
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Zhang, Cong
影响因子：
3.1
作者：
Martin Velez, Leandro;Adriana Abruzzese, Giselle;Beatriz Motta, Alicia
通讯作者：
Beatriz Motta, Alicia
影响因子：
3.1
作者：
Ying, Ke;Chen, Juan;Ren, Bo
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Ren, Bo
影响因子：
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作者：
Chen, Ai-Xue;Jin, Rui-Ying;Xuan, Fei-Lan
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Xuan, Fei-Lan