Basic research

Study on differentially expressed microRNA as a biomarker of polycystic ovary syndrome

  • Yu-huan WANG ,
  • Yi-cen DING ,
  • Yao-yu CAI ,
  • Ya-ni KANG
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  • 1.Shanghai Jiao Tong University School of Biomedical Engineering, Shanghai 200240, China
    2.Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
KANG Ya-ni, E-mail: kangyani@sjtu.edu.cn.

Online published: 2021-12-03

Supported by

Natural Science Foundation of Shanghai(19ZR1476100);National Infrastructures for Translational Medicine (Shanghai)(TMSK-2020-109);Interdisciplinary Program of Medical Engineering Cross Fund(YG2019GD02)

Abstract

Objective

·To explore microRNAs (miRNAs) as biomarkers of polycystic ovary syndrome (PCOS) and the biological significance in the pathogenesis of PCOS.

Methods

·Five patients with PCOS from January 2019 to October 2019 in Renji Hospital, Shanghai Jiao Tong University School of Medicine were selected as the observation group, and 5 healthy women were selected as the control group. Granulosa cells from 2 groups were collected and RNA was extracted by TRIzol method. TruSeq Small RNA Library Prep Kit was used to construct miRNA-Seq library. After the quality inspection of the library, NextSeq500 was used for high-throughput sequencing. Bioinformatics data analysis was performed on the sequencing results. RT-qPCR was used to verify the differential expression of candidate miRNA markers.

Results

·We finally got 20 differentially expressed miRNAs (all P<0.05). Among them, miR-196a-5p, miR-10a-5p and miR-451a were significantly up-regulated, while miR-877-5p and miR-2355-5p were significantly down-regulated. These differentially expressed miRNAs and their target genes may be involved in the transcriptional regulation mechanism of PCOS occurrence and development.

Conclusion

·Differentially expressed miRNAs have potential as PCOS biomarkers and are involved in the occurrence and development of PCOS.

Cite this article

Yu-huan WANG , Yi-cen DING , Yao-yu CAI , Ya-ni KANG . Study on differentially expressed microRNA as a biomarker of polycystic ovary syndrome[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2021 , 41(11) : 1429 -1435 . DOI: 10.3969/j.issn.1674-8115.2021.11.005

References

1 Nandi A, Chen ZJ, Patel R, et al. Polycystic ovary syndrome[J]. Endocrinol Metab Clin N Am, 2014, 43(1): 123-147.
2 Zununi Vahed S, Nakhjavani M, Etemadi J, et al. Altered levels of immune-regulatory microRNAs in plasma samples of patients with lupus nephritis[J]. BioImpacts, 2018, 8(3): 177-183.
3 Závesky L, Jandáková E, Weinberger V, et al. Ovarian cancer: differentially expressed microRNAs in tumor tissue and cell-free ascitic fluid as potential novel biomarkers[J]. Cancer Invest, 2019, 37(9): 440-452.
4 Jiang JJ, Gao SS, Zhang Y. Therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of polycystic ovary syndrome[J]. Revista Da Assoc Med Brasileira 1992, 2019, 65(9): 1144-1150.
5 Chen Z, Ou H, Wu H, et al. Role of microRNA in the pathogenesis of polycystic ovary syndrome[J]. DNA Cell Biol, 2019, 38(8): 754-762.
6 Concha CF, Sir PT, Recabarren SE, et al. Epigenetics of polycystic ovary syndrome[J]. Rev Med Chil, 2017, 145(7): 907-915.
7 Legro RS, Arslanian SA, Ehrmann DA, et al. Diagnosis and treatment of polycystic ovary syndrome: an Endocrine Society clinical practice guideline[J]. J Clin Endocrinol Metab, 2013, 98(12): 4565-4592.
8 Xin H, Wang C, Liu Z. miR-196a-5p promotes metastasis of colorectal cancer via targeting IκBα[J]. BMC Cancer, 2019, 19(1): 30.
9 Pan Y, Shu X, Sun L, et al. miR?196a?5p modulates gastric cancer stem cell characteristics by targeting Smad4[J]. Int J Oncol, 2017, 50(6): 1965-1976.
10 Bao M, Pan S, Yang W, et al. Serum miR-10a-5p and miR-196a-5p as non-invasive biomarkers in non-small cell lung cancer[J]. Int J Clin Exp Pathol, 2018, 11(2): 773-780.
11 Zhao H, Yu H, Zheng J, et al. Lowly-expressed lncRNA GAS5 facilitates progression of ovarian cancer through targeting miR-196-5p and thereby regulating HOXA5[J]. Gynecol Oncol, 2018, 151(2): 345-355.
12 Dumesic DA, Lobo RA. Cancer risk and PCOS[J]. Steroids, 2013, 78(8): 782-785.
13 Harris HR, Babic A, Webb PM, et al. Polycystic ovary syndrome, oligomenorrhea, and risk of ovarian cancer histotypes: evidence from the Ovarian Cancer Association Consortium[J]. Cancer Epidemiol Biomarkers Prev, 2018, 27(2):174-182.
14 Harris HR, Terry KL. Polycystic ovary syndrome and risk of endometrial, ovarian, and breast cancer: a systematic review[J]. Fertil Res Pract, 2016, 2: 14.
15 Jiao J, Sagnelli M, Shi B, et al. Genetic and epigenetic characteristics in ovarian tissues from polycystic ovary syndrome patients with irregular menstruation resemble those of ovarian cancer[J]. BMC Endocr Disord, 2019, 19(1): 30.
16 Yan TH, Qiu C, Sun J, et al. miR-877-5p suppresses cell growth, migration and invasion by targeting cyclin dependent kinase 14 and predicts prognosis in hepatocellular carcinoma[J]. Eur Rev Med Pharmacol Sci, 2018, 22(10): 3038-3046.
17 Cheng C, Zhang ZC, Cheng FL, et al. Exosomal lncRNA RAMP2-AS1 derived from chondrosarcoma cells promotes angiogenesis through miR-2355-5p/VEGFR2 axis[J]. Oncotargets Ther, 2020, 13: 3291-3301.
18 Zhang Q, Guan F, Fan T, et al. LncRNA WDFY3-AS2 suppresses proliferation and invasion in oesophageal squamous cell carcinoma by regulating miR-2355-5p/SOCS2 axis[J]. J Cell Mol Med, 2020, 24(14): 8206-8220.
19 Iacomino G, Russo P, Stillitano I, et al. Circulating microRNAs are deregulated in overweight/obese children: preliminary results of the Ⅰ.Family study[J]. Genes Nutr, 2016, 11(1): 1-9.
20 Wang W, Yin Y, Shan X, et al. The value of plasma-based MicroRNAs as diagnostic biomarkers for ovarian cancer[J]. Am J Med Sci, 2019, 358(4): 256-267.
21 Guo L, Li YW, Zhao C, et al. RECQL4, negatively regulated by miR-10a-5p, facilitates cell proliferation and invasion via MAFB in ovarian cancer[J]. Front Oncol, 2020, 10: 524128.
22 Zota AR, Geller RJ, VanNoy BN, et al. Phthalate exposures and microRNA expression in uterine fibroids: the FORGE study[J]. Epigenetics Insights, 2020, 13: 2516865720904057.
23 Guo T, Zhang J, Yao W, et al. CircINHA resists granulosa cell apoptosis by upregulating CTGF as a CeRNA of miR-10a-5p in pig ovarian follicles[J]. Biochim Biophys Acta Gene Regul Mech, 2019, 1862(10): 194420.
24 刘宏改, 张展. 结缔组织生长因子和多囊卵巢综合征的关系[J]. 河南医学研究, 2007, 16(2): 189-192.
25 Zong S, Liu X, Zhou N, et al. E2F7, EREG, miR-451a and miR-106b-5p are associated with the cervical cancer development[J]. Arch Gynecol Obstet, 2019, 299(4): 1089-1098.
26 Díaz M, Bassols J, López-Bermejo A, et al. Low circulating levels of miR-451a in girls with polycystic ovary syndrome: different effects of randomized treatments[J]. J Clin Endocrinol Metab, 2020, 105(3): e273-e281.
27 Legro RS, Feingold KR, Anawalt B, et al. Evaluation and treatment of polycystic ovary syndrome[J]. Practice, 2000, 17(3):82-85.
28 梅玲蔚, 熊正爱. 氧化应激与多囊卵巢综合征的研究进展[J]. 广东医学, 2014, 35(8): 1282-1284.
29 Wickenheisser JK, Nelson-DeGrave VL, Hendricks KL, et al. Retinoids and retinol differentially regulate steroid biosynthesis in ovarian theca cells isolated from normal cycling women and women with polycystic ovary syndrome[J]. J Clin Endocrinol Metab, 2005, 90(8): 4858-4865.
30 王虎生, 阮祥燕, 李扬璐, 等. 丙二醛、视黄醇与多囊卵巢综合征发病机制关系的探索[J]. 首都医科大学学报, 2018, 39(4): 512-516.
31 Dal-Pizzol F, Klamt F, Benfato MS, et al. Retinol supplementation induces oxidative stress and modulates antioxidant enzyme activities in rat sertoli cells[J]. Free Radic Res, 2001, 34(4): 395-404.
32 Baillargeon JP, Nestler JE. Commentary: polycystic ovary syndrome: a syndrome of ovarian hypersensitivity to insulin?[J]. J Clin Endocrinol Metab, 2006, 91(1): 22-24.
33 Baillargeon JP, Carpentier A. Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity[J]. Fertil Steril, 2007, 88(4): 886-893.
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