Integrated analysis identified novel miRNAs and mRNA in endometriosis.

OBJECTIVES: Endometriosis is a common gynecological disease that seriously affects women's health and quality of life. However, the pathogenesis of endometriosis remains uncertain. This study aims to find the key microRNAs (miRNAs) and mRNAs and further to elucidate the pathogenesis of endometriosis. MATERIAL AND METHODS: Differentially expressed mRNAs (DEmRNAs) and the differentially expressed miRNAs (DEmiRNAs) were obtained by Gene Expression Omnibus (GEO) datasets integration analysis. Functional enrichment analysis of DEmRNAs and DEmRNAs targeted by DEmiRNAs was enforced using GeneCodis3. The DEmiRNA-DEmRNA interaction network was built using Cytoscape. The expression of candidate DEmRNA and DEmiRNA was verified using quantitative real time-polymerase chain reaction (QRT-PCR) and online datasets followed by diagnostic and immune cell infiltration analysis. RESULTS: A total of 835 (327 down-regulated and 508 up-regulated) DEmRNAs and 39 (24 down-regulated and 15 up-regulated) DEmiRNAs were identified between ectopic endometria (EC) group and eutopic endometria (EU) group. DEmRNAs targeted by DEmiRNAs were markedly enriched in cell adhesion molecules, pathways in cancer, leukocyte transendothelial migration, cytokine-cytokine receptor interaction and MAPK signaling pathway. The DEmiRNA-DEmRNA interaction network of up-regulated miRNAs was consisted of 15 miRNAs and 188 corresponding mRNAs. For down-regulated miRNAs, the DEmiRNA-DEmRNA interaction network was consisted of 24 miRNAs and 305 corresponding mRNAs. QRT-PCR validation results of IRF6, PTGER3, NTRK2, hsa-miR-449a and hsa-miR-873-5p were in line with the GEO analysis result. RF6, PTGER3 and NTRK2 had a potential diagnostic value for endometriosis. In addition, the infiltration of macrophages M2 and NK cells activated was the most significantly increased and reduced in ectopic endometrial, respectively. CONCLUSIONS: These identified DEmRNAs and DEmiRNAs may be may be associated with the pathogenesis of endometriosis. The integrated analysis of miRNA and mRNA expression profiles may provide a new perspective for understanding the mechanisms of endometriosis and developing new treatments.

Nanog-mediated stem cell properties are critical for MBNL3-associated paclitaxel resistance of ovarian cancer.

Paclitaxel (PTX) is the standard first-line treatment of ovarian cancer, but its efficacy is limited by multidrug resistance. Therefore, it is crucial to identify effective drug targets to facilitate PTX sensitivity for ovarian cancer treatment. Seventy PTX-administrated ovarian cancer patients were recruited in this study for gene expression and survival rate analyses. Muscleblind-like-3 (MBNL3) gain-of-function and loss-of-function experiments were carried out in ovarian cancer cells (parental and PTX-resistant) and xenograft model. Cancer cell viability, apoptosis, spheroids formation, Nanog gene silencing were examined and conducted to dissect the underlying mechanism of MBNL3-mediated PTX resistance. High expression of MBNL3 was positively correlated with PTX resistance and poor prognosis of ovarian cancer. MBNL3 increased cell viability and decreased apoptosis in ovarian stem-like cells, through upregulating Nanog. This study suggests the MBNL3-Nanog axis is a therapeutic target for the treatment of PTX resistance in ovarian cancer management.

Identification of critical miRNAs and mRNAs associated with polycystic ovary syndrome.

AIM: Polycystic ovary syndrome (PCOS) is a complicated endocrine and metabolic abnormality diseases common in women of child-bearing age. This study aims to screen out critical miRNAs and mRNAs associated with PCOS, which may be conducive to offer novel insights and treatment for the diseases. METHODS: Three mRNA datasets and one miRNA dataset derived from granulosa cells of patients with PCOS and normal controls were downloaded to obtain the differentially expressed mRNAs (DEmRNAs) and miRNAs (DEmiRNAs). Then, DEmiRNA-target DEmRNAs analysis and functional annotation of DEmiRNA-target DEmRNAs were performed. Quantitative real time polymerase chain reaction (qRT-PCR) validation of the expression of the selected DEmRNAs and DEmiRNAs were performed. RESULTS: A total of 1643 DEmRNAs, 88 DEmiRNAs, 2406 DEmiRNA (down)-DEmRNA (up), and 2179 DEmiRNA (up)-DEmRNA (down) pairs were obtained. The functional annotation of DEmiRNA-target DEmRNAs revealed that C-type lectin receptor signaling pathway, Steroid biosynthesis and Galactose metabolism were significantly enriched KEGG pathways. CONCLUSION: These findings may provide make contribution to understanding PCOS pathogenesis, diagnosis, or treatment.

Expanded alleles of the FMR1 gene are related to unexplained recurrent miscarriages.

Up to 50% of recurrent miscarriage cases in women occur without an underlying etiology. In the current prospective case-control study, we determined the impact of CGG trinucleotide expansions of the fragile-X mental retardation 1 (FMR1) gene in 49 women with unexplained recurrent miscarriages. Case group consisted of women with two or more unexplained consecutive miscarriages. Blood samples were obtained and checked for the presence of expanded alleles of the FMR1 gene using PCR. Patients harboring the expanded allele, with a threshold set to 40 repeats, were further evaluated by sequencing. The number of abortions each woman had, was not associated with her respective CGG repeat number (P=0.255). The repeat sizes of CGG expansion in the FMR1 gene were significantly different in the two population groups (P=0.027). All the positive cases involved intermediate zone carriers. Hence, the CGG expanded allele of the FMR1 gene might be associated with unexplained multiple miscarriages; whether such an association is coincidental or causal can be confirmed by future studies using a larger patient cohort.

Family association study between tumour necrosis factor a gene polymorphisms and polycystic ovary syndrome in Han Chinese.

Polycystic ovary syndrome (PCOS) is a complex disease involving genetic and environmental components. Tumour necrosis factor a (TNFa) is a proinflammatory cytokine in the pathogenesis of PCOS. The genetic association between polymorphisms of TNFa gene and PCOS was investigated. A family based study was conducted with 216 family trios (648 participants) having a proband with PCOS. Transmission disequilibrium test (TDT) was used to analyse the association between two single nucleotide polymorphisms (SNP) (rs1799964, rs1799724) of TNFa gene and PCOS. Minor allele frequencies of the SNP were 0.178 (rs1799964) and 0.118 (rs1799724). The two SNP were in Hardy-Weinberg equilibrium; TDT was only conducted when one parent was heterozygous. Of 216 trios, 112 trios of rs1799964 and 76 trios of rs1799724 were tested. A significant difference in transmission was found for rs1799964 (transmitted: non-transmitted = 73 : 39; χ(2) = 10.321; P = 0.0013). rs1799724 showed no evidence of an association with PCOS; risk alleles were over transmitted (transmitted: non-transmitted = 43 : 33; χ(2) = 1.316). Transmission disequilibrium of the two SNP indicated that rs1799964 may participate in the pathogenesis of PCOS in Chinese women. These data provide a basis for further studies of TNFa in the cause of PCOS.

[Relationship between single nucleotide polymorphism-56 of calpain-10 gene and glucose and lipid metabolism in polycystic ovary syndrome patients].

OBJECTIVE: To investigate the relationship between single nucleotide polymorphism-56 (SNP-56) in calpain-10 (CAPN-10) gene and polycystic ovary syndrome (PCOS) in Chinese. METHODS: The genotypes of SNP-56 of CAPN-10 were determined through polymerase chain reaction Tm-shift genotyping method in 638 local women in Shandong Province. Among them, 334 were patients with PCOS (PCOS group) and 304 were normal women (control group). The baseline parameters including levels of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2), testosterone (T) and lipid,as well as the body mass index (BMI) and waist/hip ratio (WHR) were measured. Glucose tolerance and insulin releasing before and after loading with 75 g of glucose were also assayed. RESULTS: (1) The frequencies of two allelotypes or three genotypes did not differ between PCOS women and normal women (P > 0.05). (2) In PCOS group, patients with AA genotype had a significantly higher plasma glucose of 180 minutes OGTT (5.7 +/- 2. 2)mmol/L [P < 0.01 compared to GA genotype (4.9 +/- 1.2) mmol/L, P < 0.01 compared to GG genotype (4.9 +/- 1.4) mmol/L] and serum total cholesterol (TC) level (4.9 +/- 1.0) mmol/L [P < 0.05 compared to GA genotype (4.5 +/- 0.9) mmol/L]. (3) Compared to PCOS patients with GA + GG genotype (P < 0.05, P < 0.01) or GG genotype (P < 0.05, P < 0.01), there was significantly higher attack rate of diabetes and tumor in the family history of patients with AA genotype. CONCLUSIONS: These findings suggest that CAPN-10 gene SNP-56 which may not contribute to the genetic susceptibility of PCOS plays a role in glucose and lipid metabolism in Chinese PCOS patients. It may also be correlated with attack rate of diabetes and tumor in the family history of PCOS patients.