m7G-lncRNAs are potential biomarkers for prognosis and tumor microenvironment in patients with colon cancer / 南方医科大学学报

OBJECTIVE@#To assess the value of m7G-lncRNAs in predicting the prognosis and microenvironment of colorectal cancer (CRC).@*METHODS@#We screened m7G-lncRNAs from TCGA to construct an m7G-lncRNAs risk model using multivariate Cox analysis, which was validated using ROC and C-index curves. Calibration and nomogram were used to predict the prognosis of CRC patients. Point-bar charts and K-M survival curves were used to assess the correlation of risk scores with the patients' clinical staging and prognosis. CIBERSORT and ESTIMATE were used to explore the association between the tumor microenvironment and immune cell infiltration in patients in high and low risk groups and the correlation of risk scores with microsatellite instability, stem cell index and immune checkpoint expression. A protein-protein interaction network was constructed, and the key targets regulated by m7G-lncRNAs were identified and validated in paired samples of CRC and adjacent tissues by immunoblotting.@*RESULTS@#We identified a total of 1722 m7G-lncRNAs from TCGA database, from which 12 lncRNAs were screened to construct the risk model. The AUCs of the risk model for predicting survival outcomes at 1, 3 and 5 years were 0.727, 0.747 and 0.794, respectively. The AUC of the nomogram for predicting prognosis was 0.794, and the predicted results were consistent with actual survival outcomes of the patients. The patients in the high-risk group showed more advanced tumor stages and a greater likelihood of high microsatellite instability than those in the low-risk group (P < 0.05). The tumor stemness index was negatively correlated with the risk score (r=-0.19; P=7.3e-05). Patients in the high-risk group had higher stromal cell scores (P=0.0028) and higher total scores (P=0.007) with lowered expressions of activated mast cells (r=-0.11; P=0.045) and resting CD4+ T cells (r=-0.14; P=0.01) and increased expressions of most immune checkpoints (P < 0.05). ATXN2 (P= 0.006) and G3BP1 (P=0.007) were identified as the key targets regulated by m7G-lncRNAs, and their expressions were both higher in CRC than in adjacent tissues.@*CONCLUSION@#The risk model based on 12 m7G-lncRNAs has important prognostic value for CRC and can reflect the microenvironment and the efficacy of immunotherapy in the patients.

Resonant Recognition Model Study for Interactions between SARS CoV 2 and Human Proteins

This study was devoted to the Resonant Recognition Model (RRM) analysis of SARS-CoV-2 proteins and their possible interaction with other human proteins, specifically, SARS CoV replicases and methyl transferases, were tested, via RRM analysis, for possible interactions with host CD4 T receptor proteins and prohibitins which participate in human organism response to viral infections. The following protein sequences were studied: twenty human SARS coronavirus methyltransferase proteins, eight replicase proteins, twenty-one prohibitin proteins, and eleven CD4 -T-cell surface antigens T4 proteins. Results revealed RRM peaks at f1=0.07349 and f2=0.2839. The peak at f1 was also common for interaction between SARS-CoV-2 methyl transferases and human prohibitins, where opposite phase suggest binding between these proteins during viral infection. This interaction was not supported for viral methyltransferase and human CD4 receptors (72.4 o phase shift). Viral replicases exhibited opposite phase interaction with both prohibitins and CD4 receptors. Overall, RRM revealed common RRM frequencies for both replicases and methyl transferases, and added plausibility to interactions between SARSCoV2 methyl transferase and human prohibitin, as well as between SARS Cov2 replicase and human prohibitin and CD4 T-cell receptors(AU)

Este estudio se dedicó al análisis mediante el Modelo de Reconocimiento Resonante (RRM) de las proteínas del SARS-CoV-2 y su posible interacción con otras proteínas humanas, específicamente, fueron analizadas las replicasas de SARS CoV y las metiltransferasas, mediante análisis RRM, para detectar posibles interacciones con las Proteínas del receptor CD4 T y las prohibitinas humanas, las cuales participan en la respuesta del organismo humano a las infecciones virales. Se estudiaron las siguientes secuencias de proteínas: veinte proteínas metiltransferasas del coronavirus del SARS humano, ocho replicasas, veintiuna prohibitinas y once proteínas T4 de antígenos de superficie de células T CD4. Los resultados revelaron picos de RRM en f1 = 0.07349 y f2 = 0.2839. El pico en f1 también fue común para la interacción entre las metiltransferasas del SARS-CoV-2 y las prohibitinas humanas, donde la fase opuesta sugiere la unión entre estas proteínas durante la infección viral. Esta interacción no fue apoyada para la metiltransferasa viral y los receptores CD4 humanos (cambio de fase de 72,4 o). Las réplicas virales exhibieron una interacción de fase opuesta tanto con las prohibitinas como con los receptores CD4. En general, el análisis de RRM reveló frecuencias comunes de RRM para replicasas y metiltransferasas, y apoyó plausibilidad de las interacciones entre la metiltransferasa de SARSCoV2 y la prohibitina humana, así como entre la replicasa de Cov2 del SARS con la prohibitina humana y los receptores de células T CD4(AU)

G3BP: a promising target for cancer therapy / 药学学报

G3BP (Ras-GTPase-activating protein SH3 domain binding protein), a protein which binds to RasGAP SH3 domain, belongs to RNA-binding protein family, implicating in the downstream of Ras signaling. G3BP harbors the activities of endoribonuclease and DNA helicase, and can induce stress granules formation. G3BP plays a general role in the signal pathways of cell proliferation, differentiation, apoptosis and RNA metabolism. It has been shown to be over-expressed in a number of human malignancies and has a close relationship with tumor invasion and metastasis. Given that it has been implicated in several pathways that are known to be involved in cancer biology, G3BP may provide a new target for cancer therapy.

Expression of Ras-GTPase-activating protein SH 3 domain binding protein and osteopontin in esophageal squamous carcinoma and their effects on prognosis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the expressions and significances of Ras-GTPase-activating protein SH 3 domain binding protein(G3BP) and osteopontin (OPN) proteins in esophageal squamous carcinoma (ESC).</p><p><b>METHODS</b>The expressions of G3BP and OPN proteins in 80 cases of ESC were detected by immunohistochemistry. The relationships between the 2 protein expression and tumor size, differentiation degree, TNM stage, lymph node metastasis and prognosis of ESC were also explored.</p><p><b>RESULTS</b>(1) The positive expression rate of G3BP in ESC was 71.3%, and the rate in lymphoid metastatic group was significantly higher than that in non lymphoid metastatic group (Z=-2.283, P=0.022), but no relations were found between G3BP expression and diameter of tumor, differentiation and TNM grade (P>0.05). The G3BP positive expression group had shorter survival time than G3BP negative expression group (P=0.000). (2) The positive expression rate of OPN in ESC was 100%, and the degree of OPN expression was correlated with the differentiation (chi(2)=10.766, P=0.005) and lymphoid metastasis (Z=-2.289, P=0.022), but no relationship was found between the diameter of tumor and TNM grade (P>0.05). The expression of OPN were significantly related to survivals in a negative time-dependent manner in ESC patients (P=0.000). (3) The expression of G3BP protein correlated positively with the degree of OPN expression in ESC tissue (r(s)=0.376, P=0.001).</p><p><b>CONCLUSIONS</b>The expressions of G3BP and OPN proteins have a close relationship with lymphoid metastasis and survival in ESC patients. G3BP and OPN proteins can be considered as predictors of prognosis in ESC patients.</p>

Monoclonal antibody against G3BP: preparation, characterization and its application in analysis of human tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To better understand the molecular mechanism of tumorigenesis and progression, the monoclonal antibody against G3BP (Ras-GAP SH3 binding protein), which serves as an important downstream effector of Ras signaling, was prepared, characterized and utilized in analysis of various human tumors.</p><p><b>METHODS</b>By using the prokaryotic expression vector pGEX-5X1, GST-G3BP fusion protein was expressed in E. coli BL21 under induction of IPTG. Purified GST-G3BP fusion protein was used to immunize BALB/c mice. The monoclonal antibody against G3BP was produced through conventional hybridoma method and characterized by ELISA, Western blot and immunohistochemical staining.</p><p><b>RESULTS</b>A hybridoma cell line secreting anti-G3BP IgG1 subtype antibody was obtained. Western blot and competitive inhibition assay showed that the antibody was G3BP-specific. Immunohistochemical staining demonstrated that G3BP was over-expressed in formalin-fixed and paraffin-embedded tissues of some human tumors, such as lung cancer, colon cancer, gastric cancer and breast cancer. In breast cancer specimens, the degree of G3BP expression correlated positively with the presence of lymph node metastasis and c-erbB2 expression.</p><p><b>CONCLUSIONS</b>The G3BP-specific monoclonal antibody derived from recombination protein can be used in ELISA, Western blot and immunohistochemical assay. It may provide an important tool in analysis of G3BP in in vitro and in vivo experiments. Besides, G3BP may serve as another prognostic marker for breast cancer.</p>