Expression of signal sequence receptor subunit 1 in hepatocellular carcinoma and its relationship with prognosis / 中国综合临床

Objective:To explore the expression of signal sequence receptor subunit 1 (SSR1) and its prognostic value in hepatocellular carcinoma.Methods:Search the expression data and relevant clinical data of SSR1 in hepatocellular carcinoma patients from the Cancer Genome Atlas (TCGA) database to June 20, 2021, and download relevant public data. The expression levels of SSR1 in 334 cases of hepatocellular carcinoma with complete information and data were analyzed retrospectively. The expression difference of SSR1 gene between hepatocellular carcinoma and adjacent tissues was analyzed by Wilcoxon signed rank test. Patients with hepatocellular carcinoma were divided into high expression group and low expression group based on the median value of SSR1 expression level (14.660). χ 2 test was conducted to analyze the relationship between SSR1 expression and clinicopathological features. Cox regression and Log-rank survival test were used to analyze the relationship between SSR1 gene expression, clinicopathological features and overall survival rate in patients with hepatocellular carcinoma. Univariate and multivariate Cox regression analysis were used to determine the factors affecting prognosis. Gene set enrichment analysis (GSEA) was used to predict the possible regulatory pathways. Result:Bioinformatics analysis based on TCGA database showed that the expression level of SSR1 in hepatocellular carcinoma (16.320±7.231) was significantly higher than that in normal liver tissue (7.473±1.410). The difference between groups was statistically significant ( t=8.621, P<0.001).The overall survival rate of patients with high SSR1 gene expression group was lower than that of patients with high SSR1 gene expression group (χ 2=10.1, P<0.001). The high expression of SSR1 gene was related to sex (χ 2=4.392, P=0.036), Stage (χ 2=6.264, P=0.012), T stage (χ 2=4.561, P=0.033) and Grade classification (χ 2=14.015, P<0.001). Multivariate Cox regression analysis showed that patients with high expression of SSR1 gene got worse risk of death ( HR=1.030, 95% CI:1.002-1.060, P=0.036), and SSR1 gene expression was an independent predictor of hepatocellular carcinoma. Gene set enrichment analysis showed that the high expression of SSR1 was related to ubiquitination, cell cycle, RNA degradation, mTOR signal pathway, Wnt signal pathway and MAPK signal pathway. Conclusion:SSR1 gene is significantly up-regulated in hepatocellular carcinoma, which is related to gender, Stage, T stage and Grade classification. Ubiquitination, cell cycle, RNA degradation, mTOR signal pathway, Wnt signal pathway and MAPK signal pathway may be the key pathways for SSR1 to promote the occurrence and development of hepatocellular carcinoma.

Expression Alteration of SSR in the Process of Cardiac Remodeling / 医学研究杂志

Objective To investigate the expression changes of SSR in the process of cardiac remodeling.Methods Myocardial infarction (MI) was induced by left anterior descending coronary artery ligation in mice to establish cardiac remodeling model.Mice subjected to isoproterenol (ISO) subcutaneous injection for 2 weeks to establish acute cardiac injury model.Mice subjected to aortic banding (AB) to establish a mouse model of cardiac hypertrophy.RT-PCR was used to detect the expression change of SSR in various cardiac remodeling models.Results The expression levels of SSR subunit 1 (SSR1) and 3 (SSR3) were significantly decreased in mice after 2 weeks of MI (P ＜ 0.05),and were also decreased in acute cardiac injury induced by 2 weeks of ISO injection (P ＜ 0.05),and reduced afterl week of AB operation (P ＜ 0.05).However,the expression of SSR1 and SSR3 increased at 2 weeks after AB (P ＜ 0.05),and sustained to 8 wccks after AB (P ＜ 0.05).Conclusion The expression of SSR3 and SSR1 in different models of cardiac remodeling were significantly changed,and showed dynamic changes,suggesting that it may participate in the occurrence and development of cardiac remodeling.

The signal sequence of type II porcine reproductive and respiratory syndrome virus glycoprotein 3 is sufficient for endoplasmic reticulum retention

The glycoprotein 3 (GP3) of type II porcine reproductive and respiratory syndrome virus has the characteristic domains of a membrane protein. However, this protein has been reported to be retained in the endoplasmic reticulum (ER) rather than transported to the plasma membrane of the cell. In this study, we performed confocal laser scanning microscopy analysis of variants of GP3 and foundthat the signal sequence of the GP3 led to confinement of GP3 in the ER, while the functional ortransmembrane domain did not affect its localization. Based on these results, we concludedthat the signal sequence of GP3 contains the ER retention signal, which might play an important role in assembly of viral proteins.

Cellular localization of BS69 and the identification of its functional nuclear export signal sequence / 中国病理生理杂志

AIM: To identify the novel nuclear export signal by analyzing the DNA sequences and detecting the cell localization of different adenovirus ElA - associated protein BS69 isoforms. METHODS:BS69 DNA sequences in Emsebl database were blasted and the sequence of amino acids was aligned with the typical nuclear export signal. Different BS69 isoform fragments were cloned into pcDNA3.1 vector and transfected into Cos7 cells. The BS69 localization was observed by immunostaining and the function was verified by Western blotting. RESULTS: A novel nuclear export signal was found in BS69 isoform 2 but not in isoform 1.The isoform 2 was localized in cytoplasm and isoform 1 in nucleus, which was also consistent with the DNA sequence. The isoform 2 was involved in LMP1 - activated JNK phosphorylation whereas the isoform 1 was not. CONCLUSION: Different BS69 isoforms have different cellular localization. BS69 isoform 2 is localized in cytoplasm, interacting with Epstein - Barr virus latent membrane protein 1 and may be involved in nasopharyngeal carcinoma development.However, the isoform 1 is localized in nucleus and plays important roles in transcription.

Diverse VacA Allelic Types of Helicobacter pylori in Korea and Clinical Correlation

Helicobacter pylori has a diversity of vacA allelic types. The purpose of this study was to correlate the vacA status and the clinical outcome. After constructing specific primers for the vacA signal sequence, H. pylori-positive antral biopsy specimens were examined for the vacA status in 25 gastric ulcers, 31 duodenal ulcers, 22 gastric cancers, 42 chronic gastritis, and 8 gastroduodenal ulcers. The relationship between the vacA allele and the clinical disease was examined. The vacA genotype s1c/m1 is predominant in Korea (71/128, 55.5%). Other strains including s1b or s2 were not found in this study. s1c/m1 was more prominent in duodenal ulcers, than in gastric ulcers (p=0.041) and cancer (p=0.029). Seven out of 8 patients with gastric and coexistent duodenal ulcers had the s1c/m1 allele. No statistical differences in the positive rates of the s1a/m1, s1a/m2, and s1c/m2 alleles among the disease groups were found. In conclusion, s1c/m1 is the main vacA allele in Korea and it is particularly associated with duodenal ulcers.

Helicobacter pylori vacA Mosaicism and New Primers for vacA Signal Sequence Indigenous to Korea / 대한소아소화기영양학회지

PURPOSE: Helicobacter pylori has been known to have diverse vacA allelic types. The purpose of the study was to identify vacA diversity in Korea and design new primers for signal sequence alleles indigenous to Korea. METHODS: Fifty antral biopsy specimens, which had been proven to be H. pylori-positive, were examined for vacA status; signal sequence and mid-region. After PCR amplification and DNA sequencing, vacA alleles of Korean H. pylori strains were compared with those from other countries. RESULTS: Among Korean H. pylori strains vacA alleles with all combinations of signal sequence and mid-region were found, with the exception of s1b or s2. vacA genotype s1c/m1 was predominant in Korea. We found that GGGAGCGTTR in s1a and GGGGYTATTG in s1c were the indigenous sequences to Korea and constructed the new Korean specific primers for the vacA signal sequence; VASK-F, VASK-R, S1AK-F, and S1CK-F. CONCLUSION: This study showed that s1c/m1 is the predominant type of vacA allele in Korea. We designed new primers for the vacA signal sequence.

Characterization of an unusual variant mRNA of human lysosomal alpha-mannosidase

Lysosomal alpha-mannosidase (EC 3.2.1.24) is an exoglycosidase in the glycoprotein degradation pathway and is encoded by a 3.0 kb cDNA. A 2.3 kb cDNA from a minor species of HeLa cell mRNA was discovered by RT-PCR cloning. Southern blotting and PCR analysis of the HeLa cell genomic DNA showed that the 2.3 kb message was encoded by the lysosomal alpha-mannosidase gene. Sequence comparison of the cDNA with the corresponding genomic DNA indicated that the 2.3 kb message was generated by an unusual intra-exonic joining event.