scholarly journals Identification of Key genes associated with polycystic ovary syndrome (PCOS) and ovarian cancer using an integrated bioinformatics analysis

Author(s):  
Juan Zou ◽  
Yukun Li ◽  
Nianchun Liao ◽  
Jue Liu ◽  
Qunfeng Zhang ◽  
...  

Abstract Background Accumulating evidence suggested a strong association between polycystic ovary syndrome (PCOS) and ovarian cancer (OC), but the potential molecular mechanism is still unclear. In this study, we identify unrecognized but significant genes correlated to PCOS and OC via bioinformatics. Materials and methods Multiple bioinformatic analysis, such as Differential expression analysis, Univariate Cox analysis, functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis, and Immune infiltration analysis were utilized. We further evaluated the effect of OGN on FSHR expression via immunofluorescence. Results The TCGA-OC dataset, GSE140082 (for OC) and GSE34526 (for PCOS) dataset were downloaded. 12 genes, RNF144B, LPAR3, CRISPLD2, JCHAIN, OR7E14P, IL27RA, PTPRD, STAT1, NR4A1, OGN, GALNT6 and CXCL11, were recognized as signature genes. Drug sensitive analysis was showed that OGN might be a hub gene in the progression of PCOS and OC. Experimental analysis found OGN could increase the FSHR expression, indicating OGN could regulate the hormonal response in PCOS and OC. Furthermore, correlation analysis indicated that the function of OGN might be closely related with m6A and ferroptosis. Conclusions Our study indicated 12 signatures that might involved in the prognosis significance of OC, and closely related the correlation between OC and PCOS. Furthermore, the hub gene, OGN, was a significant gene in the OC and PCOS progression via regulating the hormonal response.

2020 ◽  
Author(s):  
Chunyu Zhu ◽  
Yajun Hu ◽  
Wangdong Zheng ◽  
Yanyan Zhang ◽  
Yiting Li ◽  
...  

Abstract Background : Xiaoyao San(XYS) has been widely used in the treatment of polycystic ovary syndrome(PCOS), but its mechanism is not clear. The purpose of this study is to elucidate the mechanism of XYS in the treatment of PCOS from the aspects of active components, targets and pathways. The purpose of the study is to explore the molecular mechanism of XYS in the treatment of PCOS. Methods : TCMSP database, UniProt and Perl were used to screen and collect the active components and targets of XYS. The genes related to PCOS were searched in GeneCards database. Collect the related targets of PCOS and XYS, use STRING database and Cytoscape software to process the data visually and analyze topology, and screen the key components and targets in the network. The key targets were enriched by R Project to predict the mechanism of XYS in the treatment of PCOS. Results : 68 active components and 96 drug targets in XYS were screened out. 3648 PCOS related disease targets were collected. 66 targets of XYS for PCOS treatment were obtained after analysis. 21 key targets of NCOA2, PGR, PTGS1, PPARG and AR were constructed after topology analysis. 63 biological functions and 111 biological pathways were obtained after gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) Pathway enrichment analysis. Conclusions : XYS has the characteristics of multi-component, multi-target and multi-path. This study discussed the active components, targets and potential mechanism of XYS in the treatment of PCOS, which provided a new direction for further study of the mechanism of XYS in the treatment of PCOS, and provides more ideas for clinical treatment of PCOS.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fang Hou ◽  
Jie Li ◽  
Jie Peng ◽  
Zhenghua Teng ◽  
Jun Feng ◽  
...  

Abstract Background TMPO-AS1 is a recently characterized oncogenic lncRNA in ovarian cancer. Its role in other ovary diseases is unknown. This study explored its role in polycystic ovary syndrome (PCOS). Methods Follicular fluid was extracted from both PCOS patients and controls. The levels of TMPO-AS1 and mature and premature miR-335-5p were analyzed by RT-qPCR. The role of TMPO-AS1 in regulating miR-355-5p maturation in granulosa-like tumor (KGN) cells was analyzed by overexpression experiments. The interaction between TMPO-AS1 and premature miR-335-5p was analyzed by RNA pull-down assay. The subcellular location of TMPO-AS1 in KGN cells was analyzed by nuclear fractionation assay. The role of TMPO-AS1 and miR-335-5p in KGN cell proliferation was analyzed by BrdU assay. Results TMPO-AS1 was increased in PCOS, while mature miR-355-5p was decreased in PCOS. TMPO-AS1 overexpression decreased mature miR-355-5p level but increased premature miR-355-5p. TMPO-AS1 was localized in both nucleus and cytoplasm. TMPO-AS1 directly interacted with premature miR-355-5p in KGN cells. TMPO-AS1 increased KGN cell proliferation while miR-355-5p decreased cell proliferation. The co-transfection assay showed that TMPO-AS1 reduced the suppressive effects of miR-355-5p on cell proliferation. Conclusions TMPO-AS1 might suppress miR-335-5p maturation to participate in PCOS.


2020 ◽  
Author(s):  
Chunyue Chen ◽  
Xuejuan Jiang ◽  
Chenye Wang ◽  
Caifei Ding

Abstract Background Polycystic ovary syndrome (PCOS) is a common and complex female endocrine disorder. The pathogenesis of PCOS is not fully elucidated. Cangfu Daotan Decoction is a kind of traditional Chinese medicine prescription widely used for PCOS patients.Methods In this study, we treated two PCOS patients with Cangfu Daotan Decoction (CDD) and both patients presented favorable responses to the treatment. We performed RNA-seq to explore the underlying molecular mechanism.Results After data analysis, we found 4 differential expressed genes including S1PR1 , which has been found to be involved in islet β-cell proliferation and cell apoptosis in diabetic mouse models. We also identified 28 differential expressed transcripts including NFATC2 , CD14 and FCGR3A , which are involved in many immune processes.Conclusions After GO enrichment analysis, we found that pathways including viral gene expression and immune response are involved in the efficacy of CDD treatment. Our study provides new evidence to better understand the pathogenesis of PCOS.


2021 ◽  
Author(s):  
Valentina Guarnotta ◽  
Silvia Lucchese ◽  
Mariagrazia Irene Mineo ◽  
Donatella Mangione ◽  
Renato Venezia ◽  
...  

Objective: The aim of this study is to clarify, in girls with premature pubarche (PP), the influence of premature androgenization on the prevalence of polycystic ovary syndrome (PCOS). Design and patients: Ninety-nine PP girls, 63 who developed PCOS and 36 who did not develop PCOS, were cross-sectionally included. Clinical, anthropometric, and metabolic parameters were evaluated to find predictive factors of PCOS. Results: Young females with PP showed a PCOS prevalence of 64% and showed higher prevalence of familial history of diabetes (p= 0.004) and lower prevalence of underweight (p= 0.025) than PP-NO-PCOS. In addition, girls with PP-PCOS showed higher BMI (p<0.001), waist circumference (p<0.001), total testosterone (p= 0.026), visceral adiposity index (VAI) (p= 0.013), total cholesterol (p<0.001), LDL-cholesterol (p<0.001), non-HDL-cholesterol (p<0.001) and lower age of menarche (p=0.015), ISI-Matsuda (p<0.001), DIo (p= 0.002), HDL-cholesterol (p= 0.026) than PP-NO-PCOS. Multivariate analysis showed that WC (p=0.049), ISI-Matsuda (p<0.001), oral disposition index (DIo) (p<0.001), VAI (p<0.001), total testosterone (p<0.001) and LDL-cholesterol (p<0.001) are independent predictive factors for PCOS in girls with PP. Conclusions: Our study established a strong association between multiple risk factors and development of PCOS in PP girls. These risk factors are predominantly related to the regulation of glucose, lipid, and androgen metabolism. Among these factors, WC, ISI-Matsuda, DIo, VAI, total testosterone and LDL-cholesterol predict PCOS.


2004 ◽  
Vol 19 (12) ◽  
pp. 2742-2747 ◽  
Author(s):  
T. Sir Petermann ◽  
A. Cartes ◽  
M. Maliqueo ◽  
D. Vantman ◽  
C. Gutiérrez ◽  
...  

2019 ◽  
Vol 105 (3) ◽  
pp. e273-e281
Author(s):  
Marta Díaz ◽  
Judit Bassols ◽  
Abel López-Bermejo ◽  
Francis de Zegher ◽  
Lourdes Ibáñez

Abstract Context Polycystic ovary syndrome (PCOS) is a prevalent disorder in adolescent girls, purportedly driven by hepato-visceral fat excess, and often followed by subfertility and type 2 diabetes. Objective We studied the baseline microRNA (miRNA) profile of girls with PCOS, and the effects of a randomized treatment with an oral contraceptive (OC) or with spironolactone–pioglitazone–metformin (SPIOMET, aiming at loss of hepato-visceral fat excess) for 1 year. Design & Patients The miRNA profile was assessed by RNA sequencing in girls with PCOS who had participated in a randomized, open-label, single-center, pilot study (n = 31; age 15.7 years, body mass index (BMI) 23.1 kg/m2). Healthy age- and BMI-matched girls (n = 13) served as controls. Differentially expressed miRNAs were validated by RT-qPCR in the entire study population. Post-treatment ovulation rates were assessed by salivary progesterone in PCOS girls. Setting Endocrinology Department, University Hospital. Results Girls with PCOS, compared with controls, had markedly reduced concentrations of circulating miR-451a, miR-652-3p, miR-106b-5p, and miR-206; pathway enrichment analysis showed that these miRNAs target genes involved in energy homeostasis and cell cycle control. In the present study, miR-451a could diagnose PCOS with 100% sensitivity and 100% specificity. SPIOMET (but not OC) was accompanied by on-treatment normalization of the miRNA profile in girls with PCOS; miR-451a concentrations after 1 year on OC or SPIOMET treatment associated closely (r = 0.66; P &lt; .0001) with post-treatment ovulation rates. Conclusion SPIOMET treatment for 1 year normalizes the miRNA profile of girls with PCOS. Circulating miR-451a may become a biomarker to guide the diagnosis and treatment of PCOS in adolescence.


2021 ◽  
Vol 10 (12) ◽  
pp. 2688
Author(s):  
Yanfei Zhang ◽  
Vani C. Movva ◽  
Marc S. Williams ◽  
Ming Ta Michael Lee

Polycystic ovary syndrome (PCOS) is a complex disorder with heterogenous phenotypes and unclear etiology. A recent phenotypic clustering study identified metabolic and reproductive subtypes of PCOS. We hypothesize that the heterogeneity of PCOS manifestations reflects different mechanistic pathways and can be identified using a genetic approach. We applied k-means clustering to categorize the genome-wide significant PCOS variants into clusters based on their associations with selected quantitative traits that likely reflect PCOS etiological pathways. We evaluated the association of each cluster with PCOS-related traits and disease outcomes. We then applied Mendelian randomization to estimate the causal effects between the traits and PCOS. Three categories of variants were identified: adiposity, insulin resistant, and reproductive. Significant associations were observed for variants in the adiposity cluster with body mass index (BMI), waist circumference and breast cancer, and variants in the insulin-resistant cluster with fasting insulin, glucose values, and homeostatic model assessment of insulin resistance (HOMA-IR). Sex hormone binding globulin (SHBG) has strong association with all three clusters. Mendelian randomization suggested a causal role of BMI and SHBG on PCOS. No causal associations were observed for PCOS on disease outcomes.


2017 ◽  
Vol 27 (2) ◽  
pp. 174-182 ◽  
Author(s):  
Holly R. Harris ◽  
Ana Babic ◽  
Penelope M. Webb ◽  
Christina M. Nagle ◽  
Susan J. Jordan ◽  
...  

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