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Circular RNA as new serum metabolic biomarkers in patients with premature ovarian insufficiency

  • Gynecologic Endocrinology and Reproductive Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Objective

Quantitative real-time PCR (qPCR) is used to detect the differential expression of circular RNAs in patients of premature ovarian insufficiency (POI), to explore the new biomarkers of POI that can be detected from blood as soon as possible.

Methods

The study collected plasma samples from 30 patients in POI group and 30 normal people group who meet the inclusion criteria, who visited the gynecology clinic of The First Affiliated Hospital of Guangzhou University of Chinese Medicine from July 2019 to December 2020. Then, circRNAs in plasma were extracted for qPCR validation.

Results

1. qPCR technology was performed on hsa_circRNA_008901 and hsa_circRNA_403959, and it was found that the levels of both were considerably downregulated in POI group. Clinical evaluation showed that both hsa_circRNA_008901 and hsa_circRNA_403959 have good diagnostic value for POI.

2. According to miRNA Regulatory Element (MRE) analysis, the predicted target miRNAs of hsa_circRNA_008901 are: hsa-miR-548c-3p, hsa-miR-924, hsa-miR-4677-5p, hsa-miR-6786-3p and hsa-miR-7974; the predicted target miRNAs of hsa_circRNA_403959 are: hsa-miR-1207-5p, hsa-miR-4691-5p, hsa-miR-4763-3p, hsa-miR-6807-5p and hsa-miR-7160-5p.

Conclusion

Compared with the normal group, the expression levels of hsa_circRNA_008901 and hsa_circRNA_403959 in the POI group were downregulated, suggesting that these two circRNAs may be potential biomarkers of POI. Bioinformatics analysis indicated that hsa_circRNA_008901 and hsa_circRNA_403959 may regulate their binding miRNA through the action form of “molecular sponge”, and then regulate the signaling pathway regulated by miRNA, and ultimately affect the disease progression of POI.

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Data availability

The detailed procedures of methods, 8 figures and 4 table are attached.

References

  1. Nelson LM (2009) Clinical practice. Primary ovarian insufficiency. N Engl J Med 360(6):606–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Shi H, Li X (2018) Effect of premature ovarian insufficiency on cardiovascular disease. Chin J Pract Gynecol Obstet 34(03):248–251

    Google Scholar 

  3. Lei X, Tan X (2018) Effect of premature ovarian insufficiency on bone metabolism. Chin J Pract Gynecol Obstet 34(03):245–248

    CAS  Google Scholar 

  4. Stevenson JC, Collins P, Hamoda H et al (2021) Cardiometabolic health in premature ovarian insufficiency. Climacteric 24(5):474–480

    Article  CAS  PubMed  Google Scholar 

  5. Coulam CB, Adamson SC, Annegers JF (1986) Incidence of premature ovarian failure. Obstet Gynecol 67(4):604–606

    CAS  PubMed  Google Scholar 

  6. Golezar S, Ramezani Tehrani F, Khazaei S, Ebadi A, Keshavarz Z (2019) The global prevalence of primary ovarian insufficiency and early menopause: a meta-analysis. Climacteric 22(4):403–411

    Article  CAS  PubMed  Google Scholar 

  7. Jeck WR, Sorrentino JA, Wang K et al (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19(2):141–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO (2012) Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS ONE 7(2):e30733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? Cell 146(3):353–358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388

    Article  CAS  PubMed  Google Scholar 

  11. Zhang X, Ying X, Xu B (2020) Research progress of circular RNA in female reproductive system. J Int Reprod Health/Family Plan 39(04):308–313

    Google Scholar 

  12. Meng Y, Jiang H (2022) Research progress on circRNAs and their relationship with animal reproduction. Heilongjiang Anim Sci Vet Med 03:39–43

    Google Scholar 

  13. Cai Y, Lei X, Chen Z, Mo Z (2020) The roles of cirRNA in the development of germ cells. Acta Histochem 122(3):151506

    Article  CAS  PubMed  Google Scholar 

  14. Chen S (2019) CircRNA expression profile in plasma of patients with premature ovarian insufficiency and investigation of TCM constitution at different stages [master]. Guangzhou university of chinese medicine, Guangzhou

    Google Scholar 

  15. Chen Z, Tian Q, Qiao J et al (2017) Chinese expert consensus on clinical diagnosis and treatment of premature ovarian insufficiency. Chin J Obstet Gynecol 52(09):577–581

    CAS  Google Scholar 

  16. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2):281–297

    Article  CAS  PubMed  Google Scholar 

  17. Dandare A, Rabia G, Khan MJ (2021) In silico analysis of non-coding RNAs and putative target genes implicated in metabolic syndrome. Comput Biol Med 130:104229

    Article  CAS  PubMed  Google Scholar 

  18. Wang H, Chen X, Yang B, Xia Z, Chen Q (2020) MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/beta-catenin signaling pathway. Cancer Cell Int 20:491

    Article  PubMed  PubMed Central  Google Scholar 

  19. Liu Y, Wang S, Pan S, Yan Q, Li Y, Zhao Y (2022) Circ_0000463 contributes to the progression and glutamine metabolism of non-small-cell lung cancer by targeting miR-924/SLC1A5 signaling. J Clin Lab Anal 36(1):e24116

    Article  CAS  PubMed  Google Scholar 

  20. Dong R, Liu J, Sun W, Ping W (2020) Comprehensive analysis of aberrantly expressed profiles of lncRNAs and miRNAs with associated ceRNA Network in lung adenocarcinoma and lung squamous cell carcinoma. Pathol Oncol Res 26(3):1935–1945

    Article  CAS  PubMed  Google Scholar 

  21. Dang W, Qin Z, Fan S et al (2016) miR-1207-5p suppresses lung cancer growth and metastasis by targeting CSF1. Oncotarget 7(22):32421–32432

    Article  PubMed  PubMed Central  Google Scholar 

  22. Raitoharju E, Seppala I, Oksala N et al (2014) Blood microRNA profile associates with the levels of serum lipids and metabolites associated with glucose metabolism and insulin resistance and pinpoints pathways underlying metabolic syndrome: the cardiovascular risk in young finns study. Mol Cell Endocrinol 391(1–2):41–49

    Article  CAS  PubMed  Google Scholar 

  23. Choi JH, Kwon SM, Moon SU et al (2021) TPRG1-AS1 induces RBM24 expression and inhibits liver cancer progression by sponging miR-4691-5p and miR-3659. Liver Int 41(11):2788–2800

    Article  CAS  PubMed  Google Scholar 

  24. Nie X, He M, Wang J et al (2020) Circulating miR-4763-3p is a novel potential biomarker candidate for human adult fulminant myocarditis. Mol Ther Methods Clin Dev 17:1079–1087

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Arslan S, Bayyurt B, Engin A, Bakir M (2021) MicroRNA analysis from acute to convalescence in Crimean Congo hemorrhagic fever. J Med Virol 93(8):4729–4737

    Article  CAS  PubMed  Google Scholar 

  26. Imai F, Kishi H, Nakao K, Nishimura T, Minegishi T (2014) IL-6 up-regulates the expression of rat LH receptors during granulosa cell differentiation. Endocrinology 155(4):1436–1444

    Article  PubMed  Google Scholar 

  27. Ishiguro K, Kojima T, Taguchi O, Saito H, Muramatsu T, Kadomatsu K (1999) Syndecan-4 expression is associated with follicular atresia in mouse ovary. Histochem Cell Biol 112(1):25–33

    Article  CAS  PubMed  Google Scholar 

  28. Franke TF, Hornik CP, Segev L, Shostak GA, Sugimoto C (2003) PI3K/Akt and apoptosis: size matters. Oncogene 22(56):8983–8998

    Article  CAS  PubMed  Google Scholar 

  29. Li D, Zhou L, Sun Z (2020) Research advances in premature ovarian insufficiency-related signaling pathways. Chin J Comp Med 30(02):121–127

    Google Scholar 

  30. Maidarti M, Anderson RA, Telfer EE (2020) Crosstalk between PTEN/PI3K/Akt signalling and DNA damage in the oocyte: implications for primordial follicle activation oocyte quality ageing. Cells 9(1):200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. el Arafa SA, Zhu Q, Barakat BM et al (2009) Tangeretin sensitizes cisplatin-resistant human ovarian cancer cells through downregulation of phosphoinositide 3-kinase/Akt signaling pathway. Cancer Res 69(23):8910–8917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. McGee EA, Hsueh AJ (2000) Initial and cyclic recruitment of ovarian follicles. Endocr Rev 21(2):200–214

    CAS  Google Scholar 

  33. Salvioli S, Capri M, Valensin S et al (2006) Inflamm-aging, cytokines and aging: state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology. Curr Pharm Des 12(24):3161–3171

    Article  CAS  PubMed  Google Scholar 

  34. Lee SH, Lee JH, Oh EY et al (2013) Ethanol extract of Cnidium officinale exhibits anti-inflammatory effects in BV2 microglial cells by suppressing NF-kappaB nuclear translocation and the activation of the PI3K/Akt signaling pathway. Int J Mol Med 32(4):876–882

    Article  PubMed  Google Scholar 

  35. Huang Y, Lv Y, Qi T et al (2021) Metabolic profile of women with premature ovarian insufficiency compared with that of age-matched healthy controls. Maturitas 148:33–39

    Article  CAS  PubMed  Google Scholar 

  36. Anagnostis P, Christou K, Artzouchaltzi AM et al (2019) Early menopause and premature ovarian insufficiency are associated with increased risk of type 2 diabetes: a systematic review and meta-analysis. Eur J Endocrinol 180(1):41–50

    Article  CAS  PubMed  Google Scholar 

  37. Schultze SM, Hemmings BA, Niessen M, Tschopp O (2012) PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis. Expert Rev Mol Med 14:e1

    Article  PubMed  Google Scholar 

  38. Chi Y, Li J, Guan Y, Yang J (2010) Regulation of glucose metabolism by PI3K-Akt signaling pathway. Chin J Biochem Mol Biol 26(10):879–885

    CAS  Google Scholar 

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Funding

This research was supported by Science and Technology Program of Guangdong Province (2016A020215180) and Research Project of Traditional Chinese Medicine Bureau of Guangdong Province (20231170).

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Author notes

  1. Zhuoya Wang and Yuqi Zheng have contributed equally to this work.

Authors and Affiliations

  1. Guangzhou University of Chinese Medicine, Guangzhou, 510000, China

    Zhuoya Wang, Yuqi Zheng, Caiting Zhong, Yuyang Ou, Yu Lin & Ying Zhao

  2. The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510000, China

    Yihui Feng & Ying Zhao

  3. Nanfang Hospital, Southern Medical University, Guangzhou, 510006, China

    Yu Lin

  4. Department of Traditional Chinese Medicine, Yuzhou People’s Hospital, Xuchang, 461670, China

    Zhuoya Wang

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  1. Zhuoya Wang
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Contributions

Conception and design: YL, YZ. Acquisition of data: ZW, CZ, YO, YF. Analysis and interpretation of data: YZ; writing, review, and/or revision of the manuscript: YL, YZ.

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Correspondence to Yu Lin or Ying Zhao.

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Wang, Z., Zheng, Y., Zhong, C. et al. Circular RNA as new serum metabolic biomarkers in patients with premature ovarian insufficiency. Arch Gynecol Obstet 308, 1871–1879 (2023). https://doi.org/10.1007/s00404-023-07219-x

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  • DOI: https://doi.org/10.1007/s00404-023-07219-x

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