Generic placeholder image

Current Molecular Medicine

Author(s): Sahar Mazloomi, Vahide Mousavi, Esmat Aghadavod* and Alireza Mafi*

DOI: 10.2174/1566524023666230110151155

DownloadDownload PDF Flyer Cite As
Circular RNAs: Emerging Modulators in the Pathophysiology of Polycystic Ovary Syndrome and their Clinical Implications

Page: [153 - 166] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

Polycystic ovary syndrome (PCOS) is a prevalent endocrine/metabolic disorder in women of reproductive age. PCOS is characterized by hyperandrogenism, polycystic ovary morphology, and ovulatory dysfunction/anovulation. It involves multiple effects in patients, including granulosa/theca cell hyperplasia, menstrual disturbances, infertility, acne, obesity, insulin resistance, and cardiovascular disorders.

Biochemical analyses and the results of RNA sequencing studies in recent years have shown a type of non-coding RNAs as a splicing product known as circular RNAs (circRNAs). Several biological functions have been identified in relation to circRNAs, including a role in miRNA sponge, protein sequestration, increased parental gene expression, and translation leading to polypeptides. These circular molecules are more plentiful and specialized than other types of RNAs. For this reason, they are referred to as potential biomarkers in different diseases. Evidence suggests that circRNAs may have regulatory potentials through different signaling pathways, such as the miRNA network.

Probably most experts in the field of obstetricians are not aware of circRNAs as a useful biomarker. Therefore, this review focused on the researches that have been done on the involvement of circRNAs in PCOS and summarized recent supportive evidence, and evaluated the circRNA association and mechanisms involved in PCOS.

[1]
Bednarska S, Siejka A. The pathogenesis and treatment of polycystic ovary syndrome: What's new? Adv Clin Exp Med 2017; 26(2): 359-67.
[2]
Fitzgerald S, DiVasta A, Gooding H. An update on PCOS in adolescents. Curr Opin Pediatr 2018; 30(4): 459-65.
[http://dx.doi.org/10.1097/MOP.0000000000000636] [PMID: 29782382]
[3]
Escobar-Morreale HF. Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018; 14(5): 270-84.
[http://dx.doi.org/10.1038/nrendo.2018.24] [PMID: 29569621]
[4]
Jamilian M, Foroozanfard F, Kavossian E, et al. Carnitine and chromium co-supplementation affects mental health, hormonal, inflammatory, genetic, and oxidative stress parameters in women with polycystic ovary syndrome. J Psychosom Obstet Gynaecol 2019; 1-9.
[http://dx.doi.org/10.1080/0167482X.2018.1557144] [PMID: 30835597]
[5]
Norman RJ, Dewailly D, Legro RS, Hickey TE. Polycystic ovary syndrome. Lancet 2007; 370(9588): 685-97.
[http://dx.doi.org/10.1016/S0140-6736(07)61345-2] [PMID: 17720020]
[6]
Bani Mohammad M, Majdi Seghinsara A. Polycystic Ovary Syndrome (PCOS), Diagnostic Criteria, and AMH, Asian Pacific journal of cancer prevention. APJCP 2017; 18(1): 17-21.
[PMID: 28240001]
[7]
Trikudanathan S. Polycystic ovarian syndrome. Med Clin North Am 2015; 99(1): 221-35.
[http://dx.doi.org/10.1016/j.mcna.2014.09.003] [PMID: 25456652]
[8]
Martínez-Bermejo E, Luque-Ramírez M, Escobar-Morreale HF. Obesity and the polycystic ovary syndrome. Minerva Endocrinol 2007; 32(3): 129-40.
[PMID: 17912153]
[9]
Roe AH, Dokras A. The diagnosis of polycystic ovary syndrome in adolescents. Rev Obstet Gynecol 2011; 4(2): 45-51.
[PMID: 22102927]
[10]
Agapova S, Cameo T, Sopher A, Oberfield S. Diagnosis and challenges of polycystic ovary syndrome in adolescence. Semin Reprod Med 2014; 32(3): 194-201.
[http://dx.doi.org/10.1055/s-0034-1371091] [PMID: 24715514]
[11]
Li L, Baek KH. Molecular genetics of polycystic ovary syndrome: an update. Curr Mol Med 2015; 15(4): 331-42.
[http://dx.doi.org/10.2174/1566524015666150505160140] [PMID: 25941819]
[12]
Mu L, Sun X, Tu M, Zhang D. Non-coding RNAs in polycystic ovary syndrome: a systematic review and meta-analysis. Reprod Biol Endocrinol 2021; 19(1): 10.
[http://dx.doi.org/10.1186/s12958-020-00687-9] [PMID: 33446212]
[13]
Cocquerelle C, Mascrez B, Hétuin D, Bailleul B. Mis-splicing yields circular RNA molecules. FASEB J 1993; 7(1): 155-60.
[http://dx.doi.org/10.1096/fasebj.7.1.7678559] [PMID: 7678559]
[14]
Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One 2012; 7(2): e30733.
[http://dx.doi.org/10.1371/journal.pone.0030733] [PMID: 22319583]
[15]
Wang X, Li H, Lu Y, Cheng L. Regulatory effects of circular RNAs on host genes in human cancer. Front Oncol 2021; 10: 586163.
[http://dx.doi.org/10.3389/fonc.2020.586163] [PMID: 33643900]
[16]
Mafi A, Yadegar N, Salami M, Salami R, Vakili O, Aghadavod E. Circular RNAs; powerful microRNA sponges to overcome dia-betic nephropathy. Pathol Res Pract 2021; 227: 153618.
[http://dx.doi.org/10.1016/j.prp.2021.153618] [PMID: 34649056]
[17]
Huang A, Zheng H, Wu Z, Chen M, Huang Y. Circular RNA-protein interactions: functions, mechanisms, and identification. Theranostics 2020; 10(8): 3503-17.
[http://dx.doi.org/10.7150/thno.42174] [PMID: 32206104]
[18]
Liu KS, Pan F, Mao XD, Liu C, Chen YJ. Biological functions of circular RNAs and their roles in occurrence of reproduction and gynecological diseases. Am J Transl Res 2019; 11(1): 1-15.
[PMID: 30787966]
[19]
Bartel DP. MicroRNAs. Cell 2004; 116(2): 281-97.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[20]
Ojha R, Nandani R, Chatterjee N, Prajapati VK. Emerging role of circular RNAs as potential biomarkers for the diagnosis of human diseases. Adv Exp Med Biol 2018; 1087: 141-57.
[http://dx.doi.org/10.1007/978-981-13-1426-1_12] [PMID: 30259364]
[21]
Greene J, Baird AM, Brady L, et al. Circular RNAs: biogenesis, function and role in human diseases. Front Mol Biosci 2017; 4: 38.
[http://dx.doi.org/10.3389/fmolb.2017.00038] [PMID: 28634583]
[22]
Xu HP, Ma XY, Yang C, Circular RNA. Circular RNA TLK1 promotes sepsis-associated acute kidney injury by regulating inflam-mation and oxidative stress through miR-106a-5p/HMGB1 axis. Front Mol Biosci 2021; 8: 660269.
[http://dx.doi.org/10.3389/fmolb.2021.660269] [PMID: 34250012]
[23]
Brozzi F, Regazzi R. Circular RNAs as novel regulators of β-cell functions under physiological and pathological conditions. Int J Mol Sci 2021; 22(4): 1503.
[http://dx.doi.org/10.3390/ijms22041503] [PMID: 33546109]
[24]
Gomes A, Nolasco S, Soares H. Non-coding RNAs: multi-tasking molecules in the cell. Int J Mol Sci 2013; 14(8): 16010-39.
[http://dx.doi.org/10.3390/ijms140816010] [PMID: 23912238]
[25]
St Laurent G, Wahlestedt C, Kapranov P. The Landscape of long noncoding RNA classification. Trends Genet 2015; 31(5): 239-51.
[http://dx.doi.org/10.1016/j.tig.2015.03.007] [PMID: 25869999]
[26]
Tang M, Kui L, Lu G, Chen W. Disease-associated circular RNAs: From biology to computational identification. BioMed Res Int 2020; 2020: 1-21.
[http://dx.doi.org/10.1155/2020/6798590] [PMID: 32908906]
[27]
Hsu MT, Coca-Prados M. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature 1979; 280(5720): 339-40.
[http://dx.doi.org/10.1038/280339a0] [PMID: 460409]
[28]
Enuka Y, Lauriola M, Feldman ME, Sas-Chen A, Ulitsky I, Yarden Y. Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor. Nucleic Acids Res 2016; 44(3): 1370-83.
[http://dx.doi.org/10.1093/nar/gkv1367] [PMID: 26657629]
[29]
Han B, Chao J, Yao H. Circular RNA and its mechanisms in disease: From the bench to the clinic. Pharmacol Ther 2018; 187: 31-44.
[http://dx.doi.org/10.1016/j.pharmthera.2018.01.010] [PMID: 29406246]
[30]
Zaphiropoulos PG. Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis. Mol Cell Biol 1997; 17(6): 2985-93.
[http://dx.doi.org/10.1128/MCB.17.6.2985] [PMID: 9154796]
[31]
Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L. Complementary sequence-mediated exon circularization. Cell 2014; 159(1): 134-47.
[http://dx.doi.org/10.1016/j.cell.2014.09.001] [PMID: 25242744]
[32]
Conn SJ, Pillman KA, Toubia J, et al. The RNA binding protein quaking regulates formation of circRNAs. Cell 2015; 160(6): 1125-34.
[http://dx.doi.org/10.1016/j.cell.2015.02.014] [PMID: 25768908]
[33]
Bachmayr-Heyda A, Reiner AT, Auer K, et al. Correlation of circular RNA abundance with proliferation – exemplified with colo-rectal and ovarian cancer, idiopathic lung fibrosis and normal human tissues. Sci Rep 2015; 5(1): 8057.
[http://dx.doi.org/10.1038/srep08057] [PMID: 25624062]
[34]
Suzuki H, Zuo Y, Wang J, Zhang MQ, Malhotra A, Mayeda A. Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res 2006; 34(8): e63-3.
[http://dx.doi.org/10.1093/nar/gkl151] [PMID: 16682442]
[35]
Wan L, Zhang L, Fan K, Cheng ZX, Sun QC, Wang JJ. Circular RNA-ITCH suppresses lung cancer proliferation via inhibiting the Wnt/β-catenin pathway. BioMed Res Int 2016; 2016: 1-11.
[http://dx.doi.org/10.1155/2016/1579490] [PMID: 27642589]
[36]
Park OH, Ha H, Lee Y, et al. Endoribonucleolytic Cleavage of m6A-Containing RNAs by RNase P/MRP Complex. Mol Cell 2019; 74(3): 494-507.
[http://dx.doi.org/10.1016/j.molcel.2019.02.034] [PMID: 30930054]
[37]
Liu CX, Li X, Nan F, et al. Structure and Degradation of Circular RNAs Regulate PKR Activation in Innate Immunity. Cell 2019; 177(4): 865-80.
[http://dx.doi.org/10.1016/j.cell.2019.03.046] [PMID: 31031002]
[38]
Fischer JW, Busa VF, Shao Y, Leung AKL. Structure-Mediated RNA Decay by UPF1 and G3BP1. Mol Cell 2020; 78(1): 70-84.e6.
[http://dx.doi.org/10.1016/j.molcel.2020.01.021] [PMID: 32017897]
[39]
Zhao M, Xu J, Zhong S, et al. Expression profiles and potential functions of circular RNAs in extracellular vesicles isolated from radioresistant glioma cells. Oncol Rep 2019; 41(3): 1893-900.
[http://dx.doi.org/10.3892/or.2019.6972] [PMID: 30664179]
[40]
Bartel DP. MicroRNAs: Target recognition and regulatory functions. Cell 2009; 136(2): 215-33.
[41]
Capel B, Swain A, Nicolis S, et al. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell 1993; 73(5): 1019-30.
[http://dx.doi.org/10.1016/0092-8674(93)90279-Y] [PMID: 7684656]
[42]
Peng L, Chen G, Zhu Z, et al. Circular RNA ZNF609 functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-150-5p in Hirschsprung’s disease. Oncotarget 2017; 8(1): 808-18.
[http://dx.doi.org/10.18632/oncotarget.13656] [PMID: 27903978]
[43]
Zheng Q, Bao C, Guo W, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun 2016; 7(1): 11215.
[http://dx.doi.org/10.1038/ncomms11215] [PMID: 27050392]
[44]
Wang R, Zhang S, Chen X, et al. EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis. Mol Cancer 2018; 17(1): 166.
[http://dx.doi.org/10.1186/s12943-018-0911-0] [PMID: 30470262]
[45]
Chen J, Li Y, Zheng Q, et al. Circular RNA profile identifies circPVT1 as a proliferative factor and prognostic marker in gastric cancer. Cancer Lett 2017; 388: 208-19.
[http://dx.doi.org/10.1016/j.canlet.2016.12.006] [PMID: 27986464]
[46]
Abdelmohsen K, Kuwano Y, Kim HH, Gorospe M. Posttranscriptional gene regulation by RNA-binding proteins during oxida-tive stress: implications for cellular senescence. Biol Chem 2008; 389(3): 243-55.
[http://dx.doi.org/10.1515/BC.2008.022]
[47]
Wang X, Fang L. Advances in circular RNAs and their roles in breast Cancer. J Exp Clin Cancer Res 2018; 37(1): 206.
[http://dx.doi.org/10.1186/s13046-018-0870-8] [PMID: 30157902]
[48]
Du WW, Yang W, Chen Y, et al. Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J 2017; 38(18): 1402-12.
[PMID: 26873092]
[49]
Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 2016; 44(6): 2846-58.
[http://dx.doi.org/10.1093/nar/gkw027] [PMID: 26861625]
[50]
Ruan Y, Li Z, Shen Y, Li T, Zhang H, Guo J. Functions of circular RNAs and their potential applications in gastric cancer. Expert Rev Gastroenterol Hepatol 2020; 14(2): 85-92.
[http://dx.doi.org/10.1080/17474124.2020.1715211] [PMID: 31922886]
[51]
Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Molecular Cell 2017; 66(1): 22-37.
[52]
Yang Y, Gao X, Zhang M, et al. Novel role of FBXW7 circular RNA in repressing glioma tumorigenesis. J Natl Cancer Inst 2018; 110(3): 304-15.
[http://dx.doi.org/10.1093/jnci/djx166] [PMID: 28903484]
[53]
Zhang M, Huang N, Yang X, et al. A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumor-igenesis. Oncogene 2018; 37(13): 1805-14.
[http://dx.doi.org/10.1038/s41388-017-0019-9] [PMID: 29343848]
[54]
Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 2015; 22(3): 256-64.
[http://dx.doi.org/10.1038/nsmb.2959] [PMID: 25664725]
[55]
Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell 2013; 51(6): 792-806.
[http://dx.doi.org/10.1016/j.molcel.2013.08.017] [PMID: 24035497]
[56]
Chen N, Zhao G, Yan X, et al. A novel FLI1 exonic circular RNA promotes metastasis in breast cancer by coordinately regulat-ing TET1 and DNMT1. Genome Biol 2018; 19(1): 218.
[http://dx.doi.org/10.1186/s13059-018-1594-y] [PMID: 30537986]
[57]
Olovnikov AM. Eco-crossover, or environmentally regulated crossing-over, and natural selection are two irreplaceable drivers of adaptive evolution: Eco-crossover hypothesis. Biosystems 2022; 218: 104706.
[http://dx.doi.org/10.1016/j.biosystems.2022.104706] [PMID: 35643186]
[58]
Dhakal S, Sapkota K, Huang F, Rangachari V. Cloning, expression and purification of the low-complexity region of RanBP9 protein. Protein Expr Purif 2020; 172: 105630.
[http://dx.doi.org/10.1016/j.pep.2020.105630] [PMID: 32217127]
[59]
Wang Z, Gu J, Yan A, Li K. Downregulation of circ-RANBP9 in laryngeal cancer and its clinical significance. Ann Transl Med 2021; 9(6): 484.
[http://dx.doi.org/10.21037/atm-21-567] [PMID: 33850881]
[60]
Yang X, Ye T, Liu H, et al. Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer. Mol Cancer 2021; 20(1): 4.
[http://dx.doi.org/10.1186/s12943-020-01300-8] [PMID: 33397425]
[61]
Li M, Liu M, Bin Y, Xia J. Prediction of circRNA-disease associations based on inductive matrix completion. BMC Med Genomics 2020; 13(S5): 42.
[http://dx.doi.org/10.1186/s12920-020-0679-0] [PMID: 32241268]
[62]
Zhang C, Liu J, Lai M, et al. Circular RNA expression profiling of granulosa cells in women of reproductive age with polycystic ovary syndrome. Arch Gynecol Obstet 2019; 300(2): 431-40.
[http://dx.doi.org/10.1007/s00404-019-05129-5] [PMID: 30937532]
[63]
Lu X, Gao H, Zhu B, Lin G. Circular RNA circ_RANBP9 exacerbates polycystic ovary syndrome via microRNA-136-5p/XIAP axis. Bioengineered 2021; 12(1): 6748-58.
[http://dx.doi.org/10.1080/21655979.2021.1964157] [PMID: 34546853]
[64]
Wang C, Tang D, Wang H, et al. Circular RNA hsa_circ_0030018 acts as a sponge of miR‐599 to aggravate esophageal carci-noma progression by regulating ENAH expression. J Cell Biochem 2020; 121(8-9): 3730-8.
[http://dx.doi.org/10.1002/jcb.29507] [PMID: 31736156]
[65]
Song D, Ye L, Xu Z, Jin Y, Zhang L. CircRNA hsa_circ_0030018 regulates the development of glioma via regulating the miR-1297/RAB21 axis. Neoplasma 2021; 68(2): 391-403.
[http://dx.doi.org/10.4149/neo_2020_200702N682] [PMID: 33440987]
[66]
Shao Y, Yang Z, Miao W, Yu X, Wu Y, Pu Y. circ_0030018 promotes glioma proliferation and metastasis. Transl Neurosci 2021; 12(1): 260-72.
[http://dx.doi.org/10.1515/tnsci-2020-0175] [PMID: 34150336]
[67]
Chu Y, Hu X, Wang G, Wang Z, Wang Y. Downregulation of miR-136 promotes the progression of osteosarcoma and is associated with the prognosis of patients with osteosarcoma. Oncol Lett 2019; 17(6): 5210-8.
[http://dx.doi.org/10.3892/ol.2019.10203] [PMID: 31186737]
[68]
Zhang C, Wang L, Chen J, Song F, Guo Y. Differential expression of miR-136 in gestational diabetes mellitus mediates the high-glucose-induced trophoblast cell injury through targeting E2F1. Int J Genomics 2020; 2020: 1-10.
[http://dx.doi.org/10.1155/2020/3645371] [PMID: 33150164]
[69]
Ji L, Zhang L, Li Y, et al. MiR-136 contributes to pre-eclampsia through its effects on apoptosis and angiogenesis of mesen-chymal stem cells. Placenta 2017; 50: 102-9.
[http://dx.doi.org/10.1016/j.placenta.2017.01.102] [PMID: 28161054]
[70]
Xu J, Qu Q, Liu B, Shen L. The circular RNA circ_0030018/miR-136/migration and invasion enhancer 1 (MIEN1) axis promotes the progression of polycystic ovary syndrome. Bioengineered 2022; 13(3): 5999-6011.
[http://dx.doi.org/10.1080/21655979.2022.2041796] [PMID: 35184658]
[71]
Kushwaha PP, Gupta S, Singh AK, Kumar S. Emerging role of migration and invasion enhancer 1 (MIEN1) in cancer progres-sion and metastasis. Front Oncol 2019; 9: 868.
[http://dx.doi.org/10.3389/fonc.2019.00868] [PMID: 31552186]
[72]
Ren H, Qi Y, Yin X, Gao J. miR-136 targets MIEN1 and involves the metastasis of colon cancer by suppressing epithelial-to-mesenchymal transition. OncoTargets Ther 2017; 11: 67-74.
[http://dx.doi.org/10.2147/OTT.S113359] [PMID: 29339925]
[73]
Ma Z, Zhao H, Zhang Y, Liu X, Hao C. Novel circular RNA expression in the cumulus cells of patients with polycystic ovary syndrome. Arch Gynecol Obstet 2019; 299(6): 1715-25.
[http://dx.doi.org/10.1007/s00404-019-05122-y] [PMID: 30941555]
[74]
Sun X, Liu X, Liu B, Li S, Zhang D, Guo H. Serum- and glucocorticoid-regulated protein kinase 3 overexpression promotes tumor development and aggression in breast cancer cells. Oncol Lett 2016; 12(1): 437-44.
[http://dx.doi.org/10.3892/ol.2016.4638] [PMID: 27429652]
[75]
Wu M, Huang C, Huang X, Liang R, Feng Y, Luo X. MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma. Oncol Rep 2017; 38(4): 2173-81.
[http://dx.doi.org/10.3892/or.2017.5900] [PMID: 28849156]
[76]
Yao L, Li M, Hu J, Wang W, Gao M. miRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS. Reproduction 2018; 156(5): 439-49.
[http://dx.doi.org/10.1530/REP-18-0229] [PMID: 30328340]
[77]
Xu L, Xiong F, Bai Y, et al. Circ_0043532 regulates miR-182/SGK3 axis to promote granulosa cell progression in polycystic ovary syndrome. Reprod Biol Endocrinol 2021; 19(1): 167.
[http://dx.doi.org/10.1186/s12958-021-00839-5] [PMID: 34740363]
[78]
Stanciu GD, Luca A, Rusu RN, et al. Alzheimer’s disease pharmacotherapy in relation to cholinergic system involvement. Biomolecules 2019; 10(1): 40.
[http://dx.doi.org/10.3390/biom10010040] [PMID: 31888102]
[79]
Filali M, Frydman N, Belot MP, et al. Oocyte in-vitro maturation: BCL2 mRNA content in cumulus cells reflects oocyte competen-cy. Reprod Biomed Online 2009; 19 (Suppl. 4): 71-84.
[http://dx.doi.org/10.1016/S1472-6483(10)61071-1] [PMID: 20034411]
[80]
Chen Y, Miao J, Lou G. Knockdown of circ-FURIN suppresses the proliferation and induces apoptosis of granular cells in polycystic ovary syndrome via miR-195-5p/BCL2 axis. J Ovarian Res 2021; 14(1): 156.
[http://dx.doi.org/10.1186/s13048-021-00891-0] [PMID: 34784951]
[81]
Xu X, Guan R, Gong K, Xie H, Shi L. Circ_FURIN knockdown assuages Testosterone-induced human ovarian granulosa-like tumor cell disorders by sponging miR-423-5p to reduce MTM1 expression in polycystic ovary syndrome. Reprod Biol Endocrinol 2022; 20(1): 32.
[http://dx.doi.org/10.1186/s12958-022-00891-9] [PMID: 35177076]
[82]
Guan X, Chen S, Liu Y, Wang L, Zhao Y, Zong ZH. PUM1 promotes ovarian cancer proliferation, migration and invasion. Biochem Biophys Res Commun 2018; 497(1): 313-8.
[http://dx.doi.org/10.1016/j.bbrc.2018.02.078] [PMID: 29428722]
[83]
Deng L, Chen Q, Xie J, Wei W, Hui H. circPUM1 promotes polycystic ovary syndrome progression by sponging to miR-760. Gene 2020; 754: 144903.
[http://dx.doi.org/10.1016/j.gene.2020.144903] [PMID: 32540374]
[84]
Chen J, Xu S, Chen S, et al. CircPUM1 promotes the malignant behavior of lung adenocarcinoma by regulating miR-326. Biochem Biophys Res Commun 2019; 508(3): 844-9.
[http://dx.doi.org/10.1016/j.bbrc.2018.11.176] [PMID: 30528736]
[85]
Guan X, Zong Z, Liu Y, Chen S, Wang L, Zhao Y. circPUM1 promotes tumorigenesis and progression of ovarian cancer by sponging mir-615-5p and mir-6753-5p. Mol Ther Nucleic Acids 2019; 18: 882-92.
[http://dx.doi.org/10.1016/j.omtn.2019.09.032] [PMID: 31751911]
[86]
Zhao C, Zhou Y, Shen X, et al. Circular RNA expression profiling in the fetal side of placenta from maternal polycystic ovary syndrome and circ_0023942 inhibits the proliferation of human ovarian granulosa cell. Arch Gynecol Obstet 2020; 301(4): 963-71.
[http://dx.doi.org/10.1007/s00404-020-05495-5] [PMID: 32193602]
[87]
Han B, Zhao J, Wang W, Li Z, He A, Song X. Cdc42 promotes schwann cell proliferation and migration through Wnt/β-catenin and p38 MAPK signaling pathway after sciatic nerve injury. Neurochem Res 2017; 42(5): 1317-24.
[http://dx.doi.org/10.1007/s11064-017-2175-2] [PMID: 28097464]
[88]
Peng Y, Chen FF, Ge J, et al. miR-429 inhibits differentiation and promotes proliferation in porcine preadipocytes. Int J Mol Sci 2016; 17(12): 2047.
[http://dx.doi.org/10.3390/ijms17122047] [PMID: 27941616]
[89]
Li C, Qin F, Xue M, et al. miR-429 and miR-424-5p inhibit cell proliferation and Ca2+ influx by downregulating CaSR in pulmo-nary artery smooth muscle cells. Am J Physiol Cell Physiol 2019; 316(1): C111-20.
[http://dx.doi.org/10.1152/ajpcell.00219.2018] [PMID: 30462536]
[90]
Huang X, Wu B, Chen M, et al. Depletion of exosomal circLDLR in follicle fluid derepresses miR-1294 function and inhibits estradiol production via CYP19A1 in polycystic ovary syndrome. Aging (Albany NY) 2020; 12(15): 15414-35.
[http://dx.doi.org/10.18632/aging.103602] [PMID: 32651991]
[91]
Panghiyangani R, Soeharso P, Andrijono DA, et al. CYP19A1 gene expression in patients with polycystic ovarian syndrome. J Hum Reprod Sci 2020; 13(2): 100-3.
[http://dx.doi.org/10.4103/jhrs.JHRS_142_18] [PMID: 32792756]
[92]
Shafique E, Choy WC, Liu Y, et al. Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK. Aging (Albany NY) 2013; 5(7): 515-30.
[http://dx.doi.org/10.18632/aging.100569] [PMID: 24018842]
[93]
Xu L, Ma Y, Zhang H, et al. HMGA2 regulates circular RNA ASPH to promote tumor growth in lung adenocarcinoma. Cell Death Dis 2020; 11(7): 593.
[http://dx.doi.org/10.1038/s41419-020-2726-3] [PMID: 32719345]
[94]
Qu Y, Qi L, Hao L, Zhu J. Upregulation of circ-ASPH contributes to glioma cell proliferation and aggressiveness by targeting the miR-599/AR/SOCS2-AS1 signaling pathway. Oncol Lett 2021; 21(5): 388.
[http://dx.doi.org/10.3892/ol.2021.12649] [PMID: 33777211]
[95]
Mumtaz PT, Taban Q, Dar MA, et al. Deep Insights in Circular RNAs: from biogenesis to therapeutics. Biol Proced Online 2020; 22(1): 10.
[http://dx.doi.org/10.1186/s12575-020-00122-8]
[96]
Wu G, Xia J, Yang Z, et al. CircASPH promotes KGN cells proliferation through miR-375/MAP2K6 axis in polycystic ovary syn-drome. J Cell Mol Med 2022; 26(6): 1817-25.
[http://dx.doi.org/10.1111/jcmm.16231] [PMID: 33372369]
[97]
Jia-yuan X, Wei S, Fang-fang L, Zhi-jian D, Long-he C, Sen L. miR-375 inhibits the proliferation and invasion of nasopharyn-geal carcinoma cells by suppressing PDK1. BioMed Res Int 2020; 2020: 1-2.
[http://dx.doi.org/10.1155/2020/3595402]
[98]
Che Q, Liu M, Xu J, et al. Characterization of circular RNA expression profiles in cumulus cells from patients with polycystic ovary syndrome. Fertil Steril 2019; 111(6): 1243-1251.e1.
[http://dx.doi.org/10.1016/j.fertnstert.2019.02.023] [PMID: 30979425]
[99]
Maffioletti E, Cattaneo A, Rosso G, et al. Peripheral whole blood microRNA alterations in major depression and bipolar disor-der. J Affect Disord 2016; 200: 250-8.
[http://dx.doi.org/10.1016/j.jad.2016.04.021] [PMID: 27152760]
[100]
Greenwood EA, Pasch LA, Shinkai K, Cedars MI, Huddleston HG. Clinical course of depression symptoms and predictors of enduring depression risk in women with polycystic ovary syndrome: Results of a longitudinal study. Fertil Steril 2019; 111(1): 147-56.
[http://dx.doi.org/10.1016/j.fertnstert.2018.10.004] [PMID: 30458991]
[101]
Cooney LG, Lee I, Sammel MD, Dokras A. High prevalence of moderate and severe depressive and anxiety symptoms in poly-cystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod 2017; 32(5): 1075-91.
[http://dx.doi.org/10.1093/humrep/dex044] [PMID: 28333286]
[102]
Farrell K, Antoni MH. Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions. Fertil Steril 2010; 94(5): 1565-74.
[http://dx.doi.org/10.1016/j.fertnstert.2010.03.081] [PMID: 20471009]
[103]
Yoo JK, Kim J, Choi SJ, et al. Discovery and characterization of novel microRNAs during endothelial differentiation of human embryonic stem cells. Stem Cells Dev 2012; 21(11): 2049-57.
[http://dx.doi.org/10.1089/scd.2011.0500] [PMID: 22142236]
[104]
Ferrara N, Frantz G, LeCouter J, et al. Differential expression of the angiogenic factor genes vascular endothelial growth factor (VEGF) and endocrine gland-derived VEGF in normal and polycystic human ovaries. Am J Pathol 2003; 162(6): 1881-93.
[http://dx.doi.org/10.1016/S0002-9440(10)64322-2] [PMID: 12759245]
[105]
Li K, Zhang J, Ji C, Wang L. MiR-144-3p and its target gene β-amyloid precursor protein regulate 1-methyl-4-phenyl-1, 2-3, 6-tetrahydropyridine-induced mitochondrial dysfunction. Mol Cells 2016; 39(7): 543-9.
[http://dx.doi.org/10.14348/molcells.2016.0050] [PMID: 27329039]
[106]
Ilie IR. Advances in PCOS Pathogenesis and progression-mitochondrial mutations and dysfunction. Adv Clin Chem 2018; 86: 127-55.
[http://dx.doi.org/10.1016/bs.acc.2018.05.003] [PMID: 30144838]
[107]
Dong F, Zhang Y, Xia F, et al. Genome-wide miRNA profiling of villus and decidua of recurrent spontaneous abortion patients. Reproduction 2014; 148(1): 33-41.
[http://dx.doi.org/10.1530/REP-14-0095] [PMID: 24686457]
[108]
Banu J, Fatima P, Sultana P, et al. Association of infertile patients having polycystic ovarian syndrome with recurrent miscar-riage. Mymensingh Med J 2014; 23(4): 770-3.
[PMID: 25481599]
[109]
Cai H, Chang T, Li Y, et al. Circular DDX10 is associated with ovarian function and assisted reproductive technology outcomes through modulating the proliferation and steroidogenesis of granulosa cells. Aging (Albany NY) 2021; 13(7): 9592-612.
[http://dx.doi.org/10.18632/aging.202699] [PMID: 33742605]
[110]
Huang P, Du S, Lin Y, et al. Identification of three potential circRNA biomarkers of polycystic ovary syndrome by bioinformatics analysis and validation. Int J Gen Med 2021; 14: 5959-68.
[http://dx.doi.org/10.2147/IJGM.S324126] [PMID: 34588800]
[111]
Su ZH, Liao HH, Lu KE, et al. Hypoxia-responsive miR-346 promotes proliferation, migration, and invasion of renal cell carci-noma cells via targeting NDRG2. Neoplasma 2020; 67(5): 1002-11.
[http://dx.doi.org/10.4149/neo_2020_190917N915] [PMID: 32453597]
[112]
Kempinska-Podhorodecka A, Blatkiewicz M, Wunsch E, et al. Oncomir MicroRNA-346 is upregulated in colons of patients with primary sclerosing cholangitis. Clin Transl Gastroenterol 2020; 11(1): e00112.
[http://dx.doi.org/10.14309/ctg.0000000000000112] [PMID: 31972611]
[113]
Li M, Zeng Z, Zhang A, Ye Q, Su S, Xia T. WGCNA Analysis Identifies Polycystic Ovary Syndrome-Associated Circular RNAs That Interact with RNA-Binding Proteins and Sponge miRNAs. Int J Gen Med 2021; 14: 8737-51.
[http://dx.doi.org/10.2147/IJGM.S335108] [PMID: 34849014]
[114]
Che Q, Liu M, Zhang D, et al. Long noncoding RNA HUPCOS promotes follicular fluid androgen excess in PCOS patients via aromatase inhibition. J Clin Endocrinol Metab 2020; 105(4): 1086-97.
[http://dx.doi.org/10.1210/clinem/dgaa060] [PMID: 32016412]
[115]
Polycarpou-Schwarz M, Groß M, Mestdagh P, et al. The cancer-associated microprotein CASIMO1 controls cell proliferation and interacts with squalene epoxidase modulating lipid droplet formation. Oncogene 2018; 37(34): 4750-68.
[http://dx.doi.org/10.1038/s41388-018-0281-5] [PMID: 29765154]
[116]
Zhang T, Tian F, Huo R, Tang A, Zeng Y, Duan YG. Detection of dendritic cells and related cytokines in follicular fluid of pa-tients with polycystic ovary syndrome. Am J Reprod Immunol 2017; 78(3): e12717.
[http://dx.doi.org/10.1111/aji.12717] [PMID: 28585716]
[117]
Wang L, Peng X, Lv X, et al. High throughput circRNAs sequencing profile of follicle fluid exosomes of polycystic ovary syn-drome patients. J Cell Physiol 2019; 234(9): 15537-47.
[http://dx.doi.org/10.1002/jcp.28201] [PMID: 30779115]
[118]
Habets GGM, Scholtes EHM, Zuydgeest D, et al. Identification of an invasion-inducing gene, Tiam-1, that encodes a protein with homology to GDP-GTP exchangers for Rho-like proteins. Cell 1994; 77(4): 537-49.
[http://dx.doi.org/10.1016/0092-8674(94)90216-X] [PMID: 7999144]
[119]
Ding M, Li Y, Yang Y, et al. Elevated expression of Tiam1 is associated with poor prognosis and promotes tumor progression in pancreatic cancer. OncoTargets Ther 2018; 11: 4367-75.
[http://dx.doi.org/10.2147/OTT.S171425] [PMID: 30100742]
[120]
Ma H-L, Gong F, Tang Y, et al. Inhibition of endometrial Tiam1/Rac1 signals induced by miR-22 up-regulation leads to the fail-ure of embryo implantation during the implantation window in pregnant mice. Biol Reproduct 2015; 92(6): 1-13.
[121]
Sirmans S, Pate K. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol 2013; 6: 1-13.
[http://dx.doi.org/10.2147/CLEP.S37559] [PMID: 24379699]
[122]
Tamaddon M, Azimzadeh M, Tavangar SM. microRNAs and long non-coding RNAs as biomarkers for polycystic ovary syn-drome. J Cell Mol Med 2022; 26(3): 654-70.
[http://dx.doi.org/10.1111/jcmm.17139] [PMID: 34989136]
[123]
Strimbu K, Tavel JA. What are biomarkers? Curr Opin HIV AIDS 2010; 5(6): 463-6.
[http://dx.doi.org/10.1097/COH.0b013e32833ed177] [PMID: 20978388]
[124]
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495(7441): 333-8.
[http://dx.doi.org/10.1038/nature11928] [PMID: 23446348]
[125]
Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol 2014; 32(5): 453-61.
[http://dx.doi.org/10.1038/nbt.2890] [PMID: 24811520]
[126]
Zhang Z, Yang T, Xiao J. Circular RNAs: Promising biomarkers for human diseases. EBioMedicine 2018; 34: 267-74.
[http://dx.doi.org/10.1016/j.ebiom.2018.07.036] [PMID: 30078734]
[127]
Zhao Z, Li X, Jian D, Hao P, Rao L, Li M. Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus. Acta Diabetol 2017; 54(3): 237-45.
[http://dx.doi.org/10.1007/s00592-016-0943-0] [PMID: 27878383]
[128]
Huang ZK, Yao FY, Xu JQ, et al. Microarray expression profile of circular RNAs in peripheral blood mononuclear cells from active tuberculosis patients. Cell Physiol Biochem 2018; 45(3): 1230-40.
[http://dx.doi.org/10.1159/000487454] [PMID: 29448254]
[129]
Qian Z, Liu H, Li M, et al. Potential diagnostic power of blood circular RNA expression in active pulmonary tuberculosis. EBioMedicine 2018; 27: 18-26.
[http://dx.doi.org/10.1016/j.ebiom.2017.12.007] [PMID: 29248507]
[130]
Lashen H. Review: Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab 2010; 1(3): 117-28.
[http://dx.doi.org/10.1177/2042018810380215] [PMID: 23148156]
[131]
Nestler JE. Metformin in the treatment of infertility in polycystic ovarian syndrome: an alternative perspective. Fertil Steril 2008; 90(1): 14-6.
[http://dx.doi.org/10.1016/j.fertnstert.2008.04.073] [PMID: 18550055]