ABSTRACT
Infertility is gradually becoming a major problem affecting health worldwide, and male factors also play an important role in infertility. Extracellular vesicles (EVs) are ultramicro membranous vesicles released by cells during activation or apoptosis, which play an important role in cell communication. Relevant studies have shown that extracellular vesicles contain a variety of bioactive substances and participate in infertility related pathophysiological processes by influencing the content of intercellular transmission. Therefore, we reviewed the relationship between extracellular vesicles and male infertility, and expounded the occurrence and potential treatment of male infertility from another perspective.
ABSTRACT
The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level.HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.
ABSTRACT
OBJECTIVE@#To explore the genetic basis for a case of Lamb-Shaffer syndrome.@*METHODS@#Genomic DNA was extracted from peripheral blood samples and subjected to whole exome sequencing(WES). Suspected variant was verified by Sanger sequencing.@*RESULTS@#The patients was found to harbor a heterozygous c.1495delA(p.Thr499Glnfs*5) frameshift variant of the SOX5 gene by WES. Sanger sequencing confirmed that the same variant was a de novo variant. Based on the American College of Medical Genetics and Genomics guidelines, c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene was predicted to be pathogenic (PVS1+PS2+PM2).@*CONCLUSION@#The c.1495delA(p.Thr499Glnfs*5) variant of the SOX5 gene probably underlies the Lamb-Shaffer syndrome in this patient.
Subject(s)
Animals , Humans , Genomics , Heterozygote , Mutation , SOXD Transcription Factors/genetics , Sheep , Exome SequencingABSTRACT
Objective@#To explore an effective long non-coding RNA (lncRNA) signature in predicting the prognosis of hepatocellular carcinoma through the analysis on RNA sequencing data of hepatocellular carcinoma patients and peritumoral tissues in the Cancer Genome Atlas (TCGA) database.@*Methods@#The clinical characteristics and RNA sequencing data of 377 hepatocellular carcinoma patients were obtained from TCGA database by the end of February 2018. Then, differentially expressed lncRNAs between 50 pairs of tumor and peritumoral tissues were explored using student’s t-test. Next, a lncRNA signature was established through LASSO Cox regression analysis. All the patients were divided into four groups (<P25, P25-, P50-, ≥P75) based on the cut-off quartiles signature. Finally, compared with the control group (<P25), the hazard ratios (HRs) of three groups (P25-, P50-, ≥P75) were calculated by using Cox regression. The survival outcomes of patients in the four groups were compared to evaluate the capacity of the lncRNA signature model.@*Results@#A total of 951 differentially expressed lncRNAs were identified between tumor and peritumoral tissues. A three-lncRNA signature, including LNCSRLR, MKLN1-AS and ZFPM2-AS1, was established to predict the prognosis of hepatocellular carcinoma patients. The outcome suggested that the death risk of the ≥P75 group was 1.57 times larger than that of the <P25 group (95%CI: 1.06-2.31, P<0.05).@*Conclusion@#The three-lncRNA signature, which established by LNCSRLR, MKLN1-AS and ZFPM2-AS1, was significantly associated with the prognosis of hepatocellular carcinoma patients based on TCGA database data.