|
|
Study on miRNA expression and target genes in serum of patients with polycystic ovary syndrome and insulin resistance and the intervention of metformin |
WANG Chenye, DING Caifei |
Department of Reproductive Medicine, Zhejiang Province Chinese and Western Medicine Hospital, Hangzhou 310003, China |
|
Cite this article: |
WANG Chenye,DING Caifei. Study on miRNA expression and target genes in serum of patients with polycystic ovary syndrome and insulin resistance and the intervention of metformin[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2020, 50(6): 465-470.
|
|
Abstract Objective: To study the effect of metformin on the serum gene expression profiles in polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). Methods: Six PCOS-IR patients were selected for the metformin treatment group and six healthy women of childbearing age as the control group. Gene chip and RT-PCR were used to study the changes of serum miRNA expression in clinically diagnosed PCOS-IR patients and the changes of serum miRNA expression after metformin intervention. For miRNAs with differential expression after screening and validation, bioinformatics method was used before gene ontology and KEGG pathway databases were used for function and pathway analysis. Results: The results of cluster analysis showed that there were differences between the untreated PCOS-IR group and the healthy control group as well as before and after metformin treatment in PCOS-IR patients. RT-PCR validated that there were 10 differentially expressed miRNAs in the untreated PCOS-IR group compared to the healthy control group, and 8 differentially expressed miRNAs before and after metformin treatment in PCOS-IR patients. GO analysis showed that the differentially expressed genes were related to transcription regulation, signal transduction, transmembrane transport, cell proliferation, cell apoptosis, cell metabolism, cell adhesion, protein phosphorylation, protein transport, multicellular biological development, coagulation function, nerve conduction, etc. KEGG analysis showed that the differentially expressed miRNAs were significantly involved in the following pathways: EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, Wnt signaling pathway, prostate cancer pathway, mTOR signaling pathway, cAMP signaling pathway, phosphatidylinositol signaling system, MAPK signaling pathway. With this method to narrow the search scope, 878 genes were obtained and related to insulin resistance and metformin therapy in PCOS patients. Conclusion: Some miRNAs were suggested to be involved in the pathogenesis of insulin resistance in PCOS patients and the treatment process of metformin.
|
Received: 10 September 2019
|
|
|
|
|
[1] AZZIZ R, DUMESIC D A, GOODARZI M O. Polycystic ovary syndrome: an ancient disorder?[J]. Fertil Steril, 2011, 95(5): 1544-1548.
[2] TAO T, LI S, ZHAO A, et al. Early impaired beta-cell function in chinese women with polycystic ovary syndrome[J]. Int J Clin Exp Pathol, 2012, 5(8): 777-786.
[3] MYKHALCHENKO K, LIZNEVA D, TROFIMOVA T, et al.
Genetics of polycystic ovary syndrome[J]. Expert Rev Mol Diagn, 2017, 17(7): 723-733.
[4] LIAO D, YU H, HAN L, et al. Association of PON1 gene polymorphisms with polycystic ovarian syndrome risk: a meta-analysis of case-control studies[J]. J Endocrinol Invest, 2018, 41(11): 1289-1300.
[5] 高贵花, 曹云霞, 易龙, 等. 胆固醇侧链裂解酶CYP11A1基因多态性与多囊卵巢综合征发病的相关性[J]. 中华妇产科杂志, 2010, 45(3): 191-196.
[6] 张敏慧, 李威, 吴效科. PCOS患者胰岛素抵抗机制及胰岛素增敏剂的促生育作用[J]. 医学研究杂志, 2009, 38(8): 10-12.
[7] Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome ( PCOS)[J]. Fertil Steril, 2004, 81(1): 19-25.
[8] 姚斐, 郁秋荣, 孔颖宏. 2型糖尿病合并抑郁患者炎性因子和胰岛素抵抗指数的变化及临床意义[J]. 中国糖尿病杂志, 2016, 24(2): 104-107.
[9] DING C F, CHEN W Q, ZHU Y T, et al. Circulating microRNAs in patients with polycystic ovary syndrome[J]. Hum Fertil, 2015, 18(1): 22-29.
[10] CHAKRABORTY C, ROY S S, HSU M J, et al. Landscape mapping of functional proteins in insulin signal transduction and insulin resistance: a network-based protein-protein interaction analysis[J]. PLoS One, 2011, 6(1): e16388.
[11] 刘宁, 刘英. Wnt信号通路在女性生殖系统中的调控作用[J]. 国际生殖健康/计划生育杂志, 2017, 36(5): 421-425.
[12] WANG Q, DAI X,YANG W, et al. Caffeine protects against alcohol induced liver fibrosis by dampening the cAMP/PKA/CREB pathway in rat hepatic stellate cells[J]. Int Immunopharmacol, 2015, 25(2): 340-352.
[13] 柏华, 宋璇婧. 二甲双胍临床应用现状及进展[J]. 临床合理用药杂志, 2019, 12(16): 175-177.
[14] 谢建将, 陈敏东, 陈曲海, 等. 二甲双胍对肺癌A549细胞增殖、迁移、侵袭能力及乳酸生成的影响[J]. 肿瘤学杂志,
2018, 24(4): 323-327. |
|
|
|