Aim: To identify the circRNAs expression pattern and roles in bisphenol A (BPA) induced germ cell apoptosis. Materials & methods: We performed circRNA/miRNA/mRNA-Seq in 120 μM BPA treated and nontreated GC-2 cells. Bioinformatic analysis, qPCR, apoptosis assays, luciferase report were done in the function analysis. Results: A large number of apoptosis related circRNAs/miRNAs/mRNAs were differentially expressed with competing endogenous RNA network constructed. Interestingly, most investigated upregulated circRNAs, including circDcbld2, circMapk1, circMpp6 and circTbc1d20 showed protective effects in antagonizing BPA toxicity, with the effects individually and synergistically observed. CircMapk1 may take its role by sponging miR-214-3p. Conclusion: circRNAs can play protective roles via sponging miRNAs in toxicity. Some circRNAs may serve as novel targets for BPA toxicity intervention or as biomarkers.
Chromosome aberration is one of the common causes of male infertility. Isodicentric chromosome is a chromosomal aberration in which two arms of a chromosome are identical in morphology and genetics and connected by two centromeres. We firstly reported a case of infertile male with nonmosaic 46, X, idic (Y) (qter‐p11.31::p11.31‐qter) but with the sex‐determining region Y (SRY). The broken site is the chromosome Y (p11.31). The patients' clinical phenotype was azoospermia and short stature. Fluorescence in situ hybridisation (FISH), chromosomal microarray comparative genomic hybridisation (array CGH) and related molecular analysis were performed. Azoospermia of this case may be caused by the abnormal chromosome structure, which leads to abnormal chromosome synapsis in spermatogenesis. Loss of genes in PAR1 and gain of genes copies in azoospermia factor (AZF) region on the Y chromosome may also contribute to the pathogenesis of azoospermia.
Background: Differential diagnosis of men with subtypes of non-obstructive azoospermia (NOA) is important for their treatment. Many genes are transcripted during meiosis. We hypothesized that some of these genes can be detected in cell-free seminal message RNA (mRNAs) (cfs-mRNA) and be developed as non-invasive biomarkers for diagnosing NOA subtypes.Objective: To screen cfs-mRNA to diagnose the completion of meiosis and predict successful sperm retrieval (SR) in men with NOA. Materials and methods: NOA patients who visited our institutes from September 2018 to December 2020 for testicular histopathological diagnosis (n = 109) or testicular SR (n = 92) were screened for participation in the study. Microarray and real-time quantitative polymerase chain reaction were used in five stages to obtain candidate cfs-mRNAs for comparisons between patients with early maturation arrest (eMA, meiosis not completed) and late MA or hypospermatogenesis (meiosis completed) and between NOA patients with successful SR and SR failure.Results: Twelve cfs-mRNAs were selected based on this comparison between men with eMA and hypospermatogenesis and their gene expression and function information. Of these, AKAP1, BOLL, TCP11 and SETX predominantly derived from testes and germ cells were proposed as candidate cfs-mRNAs. Further quantification in men with NOA demonstrated significantly higher levels of BOLL cfs-mRNA (p < 0.0001) in men with late MA or hypospermatogenesis (n = 23), compared with men with eMA (n = 51); and significantly higher levels (p < 0.0001) in patients with successful SR (n = 44) when compared with patients with SR failure (n = 37). Interestingly, with a similar cutoff value, BOLL cfs-mRNA showed high sensitivity and specificity in diagnosing late MA and hypospermatogenesis (>404 copies/ml) and predicting successful SR
BackgroundCystatin SN (cystatin 1, CST1) regulates the progression of many cancers and serves as a diagnostic marker; however, its significance in gastric cancer has not been fully elucidated. MethodsWe first analyzed the expression levels of CST1 in gastric cancer dataset in oncomine and UALCAN databases. We next analyzed the relationship between CST1 and prognosis of gastric cancer patients in KM Plotter database and downloaded TCGA GC data to verify this result. We further divided GC patients into two groups according to the level of CST1 expression for GSEA enrichment analysis. Finally, we validated the role of CST1 in gastric cancer by in vitro functional assays.ResultsWe found that CST1 expression levels in gastric cancer tissues were significantly higher than those in normal control tissues and patients with high CST1 expression had a poorer prognosis. GSEA enrichment analysis showed that the main KEGG signaling pathways enriched in the CST1 high expression group were Coagulation, Epithelial-Mesenchymal-Transition, Complement, Apoptosis, Glycolysis. In vitro functional assay confirmed that inhibition of CST1 significantly inhibited the proliferation, colony-formation,migration and invasion ability of gastric cancer cells.ConclusionsOur study shows that the expression level of CST1 correlates with the development of gastric cancer, and CST1 may be used as a diagnostic marker for poor prognosis of gastric cancer.
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