Genetic diversity, tissue-specific expression, and functional analysis of the ATP7A gene in sheep

In humans, variation of the ATP7A gene may cause cranial exostosis, which is similar to “human horn,” but the function of the ATP7A gene in sheep is still unknown. Tissue expression patterns and potential functional loci analysis of the ATP7A gene could help understand its function in sheep horn. In this study, we first identified tissue, sex, breed, and species-specific expression of the ATP7A gene in sheep based on the RNA-sequencing (RNA-seq) data. Second, the potential functional sites of the ATP7A gene were analyzed by using the whole genome sequencing (WGS) data of 99 sheep from 10 breeds. Last, the allele-specific expression of the ATP7A gene was explored. Our result showed the ATP7A gene has significantly higher expression in the big horn than in the small horn, and the ATP7A gene has high expression in the horn and skin, suggesting that this gene may be related to the horn. The PCA results show that the region around the ATP7A can distinguish horned and hornless groups to some extent, further indicating that the ATP7A may be related to horns. When compared with other species, we find seven ruminate specific amino acid sites of the ATP7A protein, which can be important to the ruminate horn. By analyzing WGS, we found 6 SNP sites with significant differences in frequency in horned and hornless populations, and most of these variants are present in the intron. But we still find some potential functional sites, including three missenses, three synonymous mutations, and four Indels. Finally, by combining the RNA-seq and WGS functional loci results, we find three mutations that showed allele-specific expression between big and small horns. This study shows that the ATP7A gene in sheep may be related to horn size, and several potential functional sites we identified here can be useful molecular markers for sheep horn breeding

Prognostic Value of Phosphotyrosine Phosphatases in Hepatocellular Carcinoma

Background/Aims: During the occurrence and progression of hepatocellular carcinoma (HCC), phosphotyrosine phosphatases (PTPs) are usually described as tumor suppressors or proto-oncogenes, and to some degree are correlated with the prognosis of HCC. Methods: A total of 321 patients from the Cancer Genome Atlas (TCGA) database and 180 patients from our validated cohort with hepatocellular carcinoma were recruited in this study. Kaplan-Meier, univariate and multivariate Cox proportional hazards model were used to evaluate the risk factors for survival. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) were applied to detect the expression levels of PTP genes. Results: After screening the data of TCGA, we identified five PTPs as HCC overall survival related PTP genes, among which only three (PTPN12, PTPRN, PTPN18) exhibited differential expression levels in our 180 paired HCC and adjacent tissues (P< 0.001). Further analysis revealed that expression of PTPN18 was positively, but PTPRN was negatively associated with prognosis of HCC both in TCGA cohort and our own cohort. As to PTPN12, results turned out to be opposite according to HBV status. In detail, higher expression of PTPN12 was associated with better outcome in HBV group but worse prognosis in Non-HBV group. Conclusion: Our results suggested that PTPN12, PTPRN and PTPN18 were independent prognostic factors in HCC

Down-Regulation of LncRNA DGCR5 Correlates with Poor Prognosis in Hepatocellular Carcinoma

Background/Aims: Long non-coding RNAs (lncRNAs) have been reported to play pivotal roles in multiple tumors and can act as tumor biomarkers. In this study, we explored the association of the expression of an lncRNA, DGCR5 with clinicopathological features and prognosis in HCC. Methods: Expression levels of DGCR5 were detected by quantitative real-time PCR (qRT-PCR) and the clinical data was obtained, including basic information, data of clinicopathology and cancer specific survival rate. Receiver operating characteristic (ROC) curve, Kaplan-Meier methods and multivariable Cox regression models were used to analyze predictive efficiency, long-term survival outcomes and risk factors. Results: DGCR5 was found down-regulated in HCC tissues (PP = 0.0035) and low expression of DGCR5 was correlated with a poor cancer specific survival (CSS) (P = 0.0019), as the overall 5-year CSS rates were 10.3% (low expression group) and 36.6% (high expression group), respectively. A stratified analysis demonstrated that low DGCR5 expression was an independent negative prognostic factor for HCC. In addition, the area under the ROC curve was 0.782 with a sensitivity of 0.633 and a specificity of 0.833. Conclusions: Our results suggest that DGCR5 may be a participator in HCC and can serve as potential biomarker for the diagnosis and prognosis in HCC

Down-Regulation of LncRNA DGCR5 Correlates with Poor Prognosis in Hepatocellular Carcinoma

Background/Aims: Long non-coding RNAs (lncRNAs) have been reported to play pivotal roles in multiple tumors and can act as tumor biomarkers. In this study, we explored the association of the expression of an lncRNA, DGCR5 with clinicopathological features and prognosis in HCC. Methods: Expression levels of DGCR5 were detected by quantitative real-time PCR (qRT-PCR) and the clinical data was obtained, including basic information, data of clinicopathology and cancer specific survival rate. Receiver operating characteristic (ROC) curve, Kaplan-Meier methods and multivariable Cox regression models were used to analyze predictive efficiency, long-term survival outcomes and risk factors. Results: DGCR5 was found down-regulated in HCC tissues (PP = 0.0035) and low expression of DGCR5 was correlated with a poor cancer specific survival (CSS) (P = 0.0019), as the overall 5-year CSS rates were 10.3% (low expression group) and 36.6% (high expression group), respectively. A stratified analysis demonstrated that low DGCR5 expression was an independent negative prognostic factor for HCC. In addition, the area under the ROC curve was 0.782 with a sensitivity of 0.633 and a specificity of 0.833. Conclusions: Our results suggest that DGCR5 may be a participator in HCC and can serve as potential biomarker for the diagnosis and prognosis in HCC

Table1_Genetic diversity, tissue-specific expression, and functional analysis of the ATP7A gene in sheep.XLSX

In humans, variation of the ATP7A gene may cause cranial exostosis, which is similar to “human horn,” but the function of the ATP7A gene in sheep is still unknown. Tissue expression patterns and potential functional loci analysis of the ATP7A gene could help understand its function in sheep horn. In this study, we first identified tissue, sex, breed, and species-specific expression of the ATP7A gene in sheep based on the RNA-sequencing (RNA-seq) data. Second, the potential functional sites of the ATP7A gene were analyzed by using the whole genome sequencing (WGS) data of 99 sheep from 10 breeds. Last, the allele-specific expression of the ATP7A gene was explored. Our result showed the ATP7A gene has significantly higher expression in the big horn than in the small horn, and the ATP7A gene has high expression in the horn and skin, suggesting that this gene may be related to the horn. The PCA results show that the region around the ATP7A can distinguish horned and hornless groups to some extent, further indicating that the ATP7A may be related to horns. When compared with other species, we find seven ruminate specific amino acid sites of the ATP7A protein, which can be important to the ruminate horn. By analyzing WGS, we found 6 SNP sites with significant differences in frequency in horned and hornless populations, and most of these variants are present in the intron. But we still find some potential functional sites, including three missenses, three synonymous mutations, and four Indels. Finally, by combining the RNA-seq and WGS functional loci results, we find three mutations that showed allele-specific expression between big and small horns. This study shows that the ATP7A gene in sheep may be related to horn size, and several potential functional sites we identified here can be useful molecular markers for sheep horn breeding.</p

T-FinFET Mobility Enhancement from Process-Induced Stress and Compact Model Development

In the advanced CMOS process lines, the process-induced stress is often used to increase carrier mobility so as to improve MOSFET performance. It also strongly affects the carrier mobility of T-FinFET as long as it is fabricated with the CMOS process as always done in experiment tunneling FET device. Here we report the effect of process-induced stress on mobility enhancement and a corresponding compact model. The layout dependence of T-FinFET’s carrier mobility due to process-induced stress is efficiently captured. The mobility model is verified for different layout dimensions for several stress-inducing process technologies through both process simulations and experimental data