LncRNA DLGAP1-AS2 overexpression associates with gastric tumorigenesis: a promising diagnostic and therapeutic target.

BACKGROUND: Aberrant expression of long noncoding RNAs (lncRNAs) is associated with the progression of human cancers, including gastric cancer (GC). The function of lncRNA DLGAP1-AS2, as a promising oncogene, has been identified in several human cancers. Therefore, this study was aimed to explore the association of DLGAP1-AS2 with gastric tumorigenesis, as well. METHODS AND RESULTS: The expression level of DLGAP1-AS2 was initially pre-evaluated in GC datasets from Gene Expression Omnibus (GEO). Moreover, qRT-PCR experiment was performed on 25 GC and 25 adjacent normal tissue samples. The Cancer Genome Atlas (TCGA) data were also analyzed for further validation. Consistent with data obtained from GEO datasets, qRT-PCR results revealed that DLGAP1-AS2 was significantly (p < 0.0032) upregulated in GC specimens compared to normal samples, which was additionally confirmed using TCGA analysis (p < 0.0001). DLGAP1-AS2 expression level was also correlated with age (p = 0.0008), lymphatic and vascular invasion (p = 0.0415) in internal samples as well as poor survival of GC patients (p = 0.00074) in GEO datasets. Also, Gene Ontology analysis illustrated that DLGAP1-AS2 may be involved in the cellular process, including hippo signaling, regulated by YAP1, as its valid downstream target, in GC samples. Moreover, ROC curve analysis showed the high accuracy of the DLGAP1-AS2 expression pattern as a diagnostic biomarker for GC. CONCLUSION: Our findings indicated that DLGAP1-AS2 might display oncogenic properties through gastric tumorigenesis and could be suggested as a therapeutic, diagnostic, and prognostic target.

Evaluation of SEPT2 and SEPT4 transcript contents in spermatozoa from men with asthenozoospermia and teratozoospermia.

BACKGROUND AND AIMS: Motility and morphological defects of spermatozoa can cause male infertility. Sperm RNAs are related to sperm quality. They are considered to have clinical values as a biomarker for assessing sperm quality and fertility potential. The annulus, located in the mammalian sperm tail, is required for motility and terminal differentiation of the spermatozoa. SEPT2, 4, 6, 7, and 12 proteins are the main components of the annulus in the sperm tail. The study aimed to evaluate SEPT2 and SEPT4 mRNA contents in the spermatozoa of patients with asthenozoospermia and teratozoospermia. METHODS: We evaluated transcript levels of SEPT2 and SEPT4 in the sperm samples of 20 asthenozoospermic, 20 teratozoospermic, and 20 normozoospermic samples using quantitative PCR. RESULTS: The SEPT2 transcript level was significantly decreased in the asthenozoospermia samples compared with the normal group (P = .013). However, SEPT4 was not significantly different between these two groups. The transcript levels of SEPT2 and SEPT4 were not statistically different between teratozoospermic and normozoospermic groups. CONCLUSION: In conclusion, downregulation of SEPT2 in patients with asthenozoospermia appears to be associated with poor sperm motility.

Long non-coding RNA-associated competing endogenous RNA axes in the olfactory epithelium in schizophrenia: a bioinformatics analysis.

The etiology of schizophrenia (SCZ), as a serious mental illness, is unknown. The significance of genetics in SCZ pathophysiology is yet unknown, and newly identified mechanisms involved in the regulation of gene transcription may be helpful in determining how these changes affect SCZ development and progression. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the olfactory epithelium (OE) samples in order to better understand the molecular regulatory processes implicated in SCZ disorders in living individuals. The Gene Expression Omnibus database was used to obtain the OE microarray dataset (GSE73129) from SCZ sufferers and control subjects, which contained information about both lncRNAs and mRNAs. The limma package of R software was used to identify the differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs). RNA interaction pairs were discovered using the Human MicroRNA Disease Database, DIANA-LncBase, and miRTarBase databases. In this study, the Pearson correlation coefficient was utilized to find positive correlations between DEmRNAs and DElncRNAs in the ceRNA network. Eventually, lncRNA-associated ceRNA axes were developed based on co-expression relations and DElncRNA-miRNA-DEmRNA interactions. This work found six potential DElncRNA-miRNA-DEmRNA loops in SCZ pathogenesis, including, SNTG2-AS1/hsa-miR-7-5p/SLC7A5, FLG-AS1/hsa-miR-34a-5p/FOSL1, LINC00960/hsa-miR-34a-5p/FOSL1, AQP4-AS1/hsa-miR-335-5p/FMN2, SOX2-OT/hsa-miR-24-3p/NOS3, and CASC2/hsa-miR-24-3p/NOS3. According to the findings, ceRNAs in OE might be promising research targets for studying SCZ molecular mechanisms. This could be a great opportunity to examine different aspects of neurodevelopment that may have been hampered early in SCZ patients.

Genetic basis of acephalic spermatozoa syndrome, and intracytoplasmic sperm injection outcomes in infertile men: a systematic scoping review.

PURPOSE: Acephalic spermatozoa syndrome (ASS) is known as a severe type of teratozoospermia, defined as semen composed of mostly headless spermatozoa that affect male fertility. In this regard, this systematic review aimed to discuss gene variants associated with acephalic spermatozoa phenotype as well as the clinical outcomes of intracytoplasmic sperm injection (ICSI) treatment for the acephalic spermatozoa-associated male infertility. METHODS: A systematic search was performed on PubMed, Embase, Scopus, and Ovid databases until May 17, 2020. This systematic scoping review was reported in terms of the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement. RESULTS: Twenty articles were included in this systematic review. Whole-exome and Sanger sequencing have helped in the identification of variants in SUN5, PMFBP1, BRDT, TSGA10, DNAH6, HOOK1, and CEP112 genes as possible causes of this phenotype in humans. The results of the ICSI are conflicting due to both positive and negative reports of ICSI outcomes. CONCLUSION: ASS has a genetic origin, and several genetic alterations related to the pathogenesis of this anomaly have been recently identified. Notably, only SUN5 and PMFBP1 mutations are well-known to be implicated in ASS. Accordingly, more functional studies are needed to confirm the pathogenicity of other variants. ICSI could provide a promising treatment for acephalic spermatozoa-associated male infertility. Besides the importance of sperm head-tail junction integrity, some other factors, whether within the sperm cell or female factors, may be involved in the ICSI outcome.

MicroRNAs association with azoospermia, oligospermia, asthenozoospermia, and teratozoospermia: a systematic review.

Infertility is a major health problem across the world. One of the main reasons for male infertility are defects in sperm. Semen analysis is the most common test utilized to evaluate male fertility and since it suffers from multiple drawbacks, reproduction scientists have tried to find new molecular markers for detecting sperm defects. MicroRNAs (miRNAs) are small molecules in cells which take part in regulating gene expression. Various studies have confirmed miRNAs to have a role in defining multiple sperm characteristics, including sperm count, motility, and morphology. In this paper, we have systematically reviewed the role of miRNAs in infertile men with sperm defects including azoospermia, oligospermia, asthenozoospermia, and teratozoospermia. Also, we have assembled various bioinformatics tools to come up with a pipeline for predicting novel miRNAs which could possibly participate in sperm count, motility, and morphology. Also, related KEGG and GO terms for predicted miRNAs have been included in order to highlight their role in sperm function. Our study emphasizes the potential role of miRNAs in male infertility and provides a general overview for future studies aiming to find robust molecular markers for this condition.