Integrative Multi-Omics Analysis of Identified SKA3 as a Candidate Oncogene Correlates with Poor Prognosis and Immune Infiltration in Lung Adenocarcinoma.

Background: Spindle and kinetochore-associated complex subunit 3 (SKA3) plays important roles in promoting the migration and the invasion of various human cancer cells. There are a few studies on SKA3 in lung adenocarcinoma (LUAD), but the in-depth analysis of the expression of SKA3 and the correlated possible immune mechanism of SKA3 in LUAD are not clear. Methods: In our study, the expression and survival data of SKA3 were analyzed in LUAD using TIMER, Oncomine, UALCAN, cBioPortal, LinkedOmics, Human Protein Atlas, and Kaplan-Meier plotter. Then, quantitative PCR was used to verify the expression differences of SKA3 between LUAD tissues of mice and the normal tissues. Results: We established that the expression of SKA3 in the LUAD group was remarkably higher than that in the normal group. Additionally, high SKA3 expression was linked to poorer survival in LUAD. Moreover, SKA3 expression had a remarkable negative correlation with the immune infiltration of B cells, macrophages, and CD4+ T cells. SKA3 was markedly negatively related to the immune type biomarkers of T cells and B cells in LUAD. The elevated expression of SKA3 with LUAD in enriched B cells, CD4+ T cells, CD8+ T cells, macrophages and Treg cells had worse prognosis, respectively. Functional network analysis showed that SKA3 regulated the mitotic cell cycle, mitosis, chromosome segregation and cell division via pathways. Conclusion: In summary, our study suggested that SKA3 was highly expressed in LUAD and SKA3 might function as a prognostic biomarker in LUAD. Besides, SKA3 may be a candidate oncogene, which correlates with poor prognosis and immune infiltration in lung adenocarcinoma.

Protein phosphatase 1 regulatory subunit 3G (PPP1R3G) correlates with poor prognosis and immune infiltration in lung adenocarcinoma.

The protein phosphatase 1 regulatory subunit 3 G (PPP1R3G) participates in many tumor biological processes; however, its effects on lung adenocarcinoma (LUAD) have not been clarified. Therefore, this study aimed to explore the correlation between PPP1R3G and the prognosis and immune invasion of LUAD. We evaluated the relationship between PPP1R3G and LUAD using a wide range of databases and analysis tools, including UALCAN, TIMER, miRDB, The Human Protein Atlas and the MethSurv database. First, we explored the mRNA and protein expression levels of PPP1R3G in LUAD, and results were validated using real-time PCR. Next, we explored the relationship between PPP1R3G expression and clinical features. Finally, Kaplan-Meier curves and Cox regression were employed to investigate the prognostic significance of PPP1R3G in LUAD. In addition, we explored the relationship between the expression of PPP1R3G and immune infiltration using the TIMER database. We analyzed the relationship between PPP1R3G and methylation using MethSurv database. Results showed that PPP1R3G expression in LUAD tissues was higher than that in normal tissues, and high expression was suggestive of a poor prognosis. Moreover, PPP1R3G expression was positively correlated with the immune infiltration of CD4 + T cells, macrophages, neutrophils, and dendritic cells. PPP1R3G copy number variations also demonstrated remarkable associations with the levels of B cells, CD4 + T cells, macrophages, neutrophils, and dendritic cells. Finally, a PPP1R3G-associated regulatory network was constructed. Overall, PPP1R3G might be a poor prognostic biomarker for LUAD and is associated with tumor immune cell infiltration.Abbreviations: LUAD: Lung adenocarcinoma; PPP1R3G: The protein phosphatase 1 regulatory subunit 3G; OS: overall survival; CI: confidence interval; CNV: copy number variance; HR: Hazard Ratio; ROC: receiver operating characteristic curve; AUC: area under the curve; TCGA: The Cancer Genome Atlas.

Marsdenia tenacssima extract and its functional components inhibits proliferation and induces apoptosis of human Burkitt leukemia/lymphoma cells in vitro and in vivo.

Burkitt lymphoma is a fast growing non-Hodgkin lymphoma that occurs primarily in young males. The causes of Burkitt lymphoma include chromosome rearrangement and virus infection, but accurate and complete reasons remain to be discovered. The available treatment for Burkitt lymphoma is chemotherapy and radiation therapy. It is a highly aggressive B-cell neoplasm with not all patients cured, in spite of current therapies. This study evaluated the effects of traditional Chinese medicine Marsdenia tenacssima (MTE) and its component compound Tenacigenoside A (TGTA) and 11α-O-benzoyl-12ß-O-acetyltenacigenin B (TGTB) on human Burkitt lymphoma growth. It was observed that MTE, TGTA or TGTB inhibited cell growth and induced apoptosis of Burkitt lymphoma cells in culture. In lymphoma bearing NOD/SCID nude mice, both TGTA and TGTB inhibited tumor growth and improved animal survival. TGTA and TGTB significantly increased tumor cell apoptosis on lymphoma bearing mice, primarily through down-regulation of BCL2 and BCL-XL and up-regulation of BID.

N-methyl-D-aspartate receptor-dependent denitrosylation of neuronal nitric oxide synthase increase the enzyme activity.

Our laboratory once reported that neuronal nitric oxide synthase (nNOS) S-nitrosylation was decreased in rat hippocampus during cerebral ischemia-reperfusion, but the underlying mechanism was unclear. In this study, we show that nNOS activity is dynamically regulated by S-nitrosylation. We found that overexpressed nNOS in HEK293 (human embryonic kidney) cells could be S-nitrosylated by exogenous NO donor GSNO and which is associated with the enzyme activity decrease. Cys(331), one of the zinc-tetrathiolate cysteines, was identified as the key site of nNOS S-nitrosylation. In addition, we also found that nNOS is highly S-nitrosylated in resting rat hippocampal neurons and the enzyme undergos denitrosylation during the process of rat brain ischemia/reperfusion. Intrestingly, the process of nNOS denitrosylation is coupling with the decrease of nNOS phosphorylation at Ser(847), a site associated with nNOS activation. Further more, we document that nNOS denitrosylation could be suppressed by pretreatment of neurons with MK801, an antagonist of NMDAR, GSNO, EGTA, BAPTA, W-7, an inhibitor of calmodulin as well as TrxR1 antisense oligonucleotide (AS-ODN) respectively. Taken together, our data demonstrate that the denitrosylation of nNOS induced by calcium ion influx is a NMDAR-dependent process during the early stage of ischemia/reperfusion, which is majorly mediated by thioredoxin-1 (Trx1) system. nNOS dephosphorylation may be induced by the enzyme denitrosylation, which suggest that S-nitrosylation/denitrosylation of nNOS may be an important mechanism in regulating the enzyme activity.