The Expression of RTN1 in Lung Adenocarcinoma and Its Effect on Immune Microenvironment / 中国肺癌杂志

BACKGROUND@#Reticulosome family gene 1 (RTN1) is a reticulosome-encoding gene associated with the endoplasmic reticulum. RTN1 plays a key role in membrane trafficking or neuroendocrine secretion of neuroendocrine cells, while RTN1 serves as a potential diagnostic/therapeutic marker for neurological diseases and cancer. However, the expression of RTN1 and its effect on the immune microenvironment in patients with lung adenocarcinoma have not been reported. In this study, we aimed to investigate the expression of RTN1 in lung adenocarcinoma and its correlation with immune infiltration and survival in lung adenocarcinoma using public databases and bioinformatics network tools.@*METHODS@#Expression levels of RTN1 mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). RTN1 protein expression was examined using the Human Protein Atlas. The clinical prognostic significance of RTN1 was analyzed using the GEPIA2 plotter database. To further confirm the potential function of RTN1, the data were analyzed using gene set enrichment analysis. In addition, We performed dimensionality-reduced clustering analysis at the single-cell sequencing level on two datasets from the Tumor Immune Single-cell Hub (TISCH) database to observe the cellular clustering of RTN1 in different types of immune cells. Using the TIMER online tool to analyze and predict the infiltration abundance of different types of immune cells in the immune microenvironment of lung adenocarcinoma patients in the TCGA cohort; TIMER and CIBERSORT were used to study the relationship between genes co-expressed with RTN1 and its associated tumor-infiltrating immune cells; finally, TIMER was used to analyze the relationship between RTN1 and immune correlations between immune checkpoints.@*RESULTS@#We found that RTN1 expression was decreased in patients with lung adenocarcinoma and was closely related to patient prognosis. RTN1 is involved in the process of phagosome formation, hematopoietic cell formation and cell adhesion, and plays an important role in T cell activation. Using cBioPortal and TCGA data to analyze, it is found that RTN1 is significantly associated with BTK, CD4, ECSF1R, MNDA, NCKAP1L and SNX20. High expression of the above genes may cause significant upregulation of CD4+ T cells, mast cells, monocytes, myeloid dendritic cells and M1 macrophages. The expression of RTN1 is closely related to the common immune checkpoints CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT and SIGLEC15 immune checkpoints.@*CONCLUSIONS@#RTN1 may act as a tumor suppressor gene and indicate better prognosis. Furthermore, RTN1 is associated with immune infiltration that may be involved in the immunotherapy response in LUAD. However, the related mechanism needs further research.

Does decreased snx10 serve as a novel risk factor in atrial fibrillation of the valvular heart disease? - a case-control study

Abstract Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia. Sorting nexin 10 (SNX10) has been reported to be an important regulator in embryonic development and human diseases, however, little is known about its role in cardiac disease. The aim of this study was to investigate the clinical significance of SNX10 expression in AF. Methods: Nineteen valvular heart disease patients with AF and nine valvular heart disease patients with sinus rhythm (SR) were enrolled. Atrial tissue samples from patients undergoing open heart surgery were examined. Atrial tissues of normal hearts were obtained from two cases' autopsies. The SNX10 expression and its associations with the degree of fibrosis were analyzed by immunohistochemistry and Masson's trichrome staining. Results: SNX10 expression was detected in the cytoplasm of cardiac cells in human myocardial tissue. The SNX10 expression level was higher in the SR group than in the AF group (P=0.023). SNX10 expression was negatively associated with the degree of fibrosis (P=0.017, Spearman rho=-0.447), the New York Heart Association degree (P=0.003, Spearman rho=-0.545), left atrial diameter (P=0.038, Spearman rho=-0.393), right atrial diameter (P=0.043, Spearman rho=-0.386), and the brain natriuretic peptide (BNP) level 24 hours after surgery (P=0.030, Spearman rho=-0.426), but not the BNP level before surgery and 72 hours after surgery. No statistical significance was observed between SNX10 and the level of troponin T and C-reactive protein. Conclusion: Decreased SNX10 might serve as a potential risk factor in AF of the valvular heart disease.

SNX10 gene mutation in infantile malignant osteopetrosis: A case report and literature review / 中南大学学报(医学版)

A case of SNX10 gene mutation in a patient with infantile malignant osteopetrosis (IMO) was admitted to Department of Pediatrics, Third Xiangya Hospital, Central South University. The patient had the symptom of anemia, hepatosplenomegaly and growth retardation. The X-ray examination suggested extensive increase of bone density throughout the body, which was clinically diagnosed as IMO. The homozygous mutation of SNX10 gene c.61C>T was found via gene sequencing. We reviewed the relevant literatures and found that anemia, visual and hearing impairment, hepatosplenomegaly are the main clinical symptoms of IMO, SNX10 gene mutation is a rare cause of IMO, and hematopoietic stem cell transplantation is an effective treatment.

Expression, purification and phosphoinositide binding specifity of recombinant human SNX7 expressed in Escherichia coli / 生物工程学报

Sorting nexins (SNXs) are a large group of proteins that contain Phox (PX) domain and involve in regulating endocytosis and endosome sorting. SNX7, a member of SNXs family, contains a PX domain and a BAR domain. In zebrafish, SNX7 is a liver-enriched anti-apoptotic protein and indispensible for the liver development. A fragment of SNX7 cDNA ((px-bar)snx7), encoding the PX domain and the BAR domain, was inserted into the expressing vector p28a, transformed into E. coli Rosseta 2 (DE3), and then induced by isopropyl β-D-1-Thiogalactopyranoside (IPTG). After affinity, ion exchange and gel filtration purification, the purity of (PX-BAR)SNX7 reached over 95%. Dynamic light scattering (DLS) experiment indicated that (PX-BAR)SNX7 was homogeneous in solution. Lipid overlay assay showed that (PX-BAR)SNX7 can bind to PtdIns(5)P, PtdIns(4,5)P2 and PtdIns(3,4,5)P3.

Sorting Nexin 17 Interacts Directly with Kinesin Superfamily KIF1B beta Protein

KIF1B beta is a member of the Kinesin superfamily proteins (KIFs), which are microtubule-dependent molecular motors that are involved in various intracellular organellar transport processes. KIF1B beta is not restricted to neuronal systems, however, is widely expressed in other tissues, even though the function of KIF1B beta is still unclear. To elucidate the KIF1B beta-binding proteins in non-neuronal cells, we used the yeast two-hybrid system, and found a specific interaction of KIF1B beta and the sorting nexin (SNX) 17. The C-terminal region of SNX17 is required for the binding with KIF1B beta. SNX17 protein bound to the specific region of KIF1B beta (813-916. aa), but not to other kinesin family members. In addition, this specific interaction was also observed in the Glutathione S-transferase pull-down assay. An antibody to SNX17 specifically co-immunoprecipitated KIF1B beta associated with SNX17 from mouse brain extracts. These results suggest that SNX17 might be involved in the KIF1B beta-mediated transport as a KIF1B beta adaptor protein.