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RNA Binding Motif Protein 8A (RBM8A) is a component of the spliceosome, which couples pre- and post-mRNA splicing events. Dysregulated expression of RBM8A has been recently discovered in hepatocellular carcinoma and gastric cancer. This study aimed to investigate the expression pattern of RBM8A protein in colon adenocarcinoma and to explore its correlation with patients' clinicopathological characteristics as well as clinical outcomes. Accordingly, we initially found that RBM8A was significantly higher in colon adenocarcinoma tissues compared to adjacent tissues on both mRNA and protein levels. Meanwhile, RBM8A protein was positively correlated with tumor size, depth of invasion, and lymph node metastasis. Furthermore, patients with increased RBM8A expression or positive lymph nodes exhibited a poorer overall survival. Consistently, immunoblotting data showed that RBM8A was higher in SW480 and SW620 colon adenocarcinoma cell lines compared to nontumorous cells. Finally, in vitro and in vivo assays elucidated the role of RBM8A on promoting colon cancer growth by using knockdown strategy. Taken together, our study demonstrated that RBM8A may act as a proto-oncogene, which could be a promising biomarker and therapeutic target in the survival prediction and treatment of colon adenocarcinoma. Keywords: RBM8A, colon adenocarcinoma, overall survival, prognosis, proliferation., Introduction Colorectal cancer is a common malignancy of the digestive system and ranks the second most common cause of cancer death in the United States (Siegel et al. 2020). The [...]

Background: T‐cell immunoglobulin and immunoreceptor tyrosine‐based inhibitory motif domain (TIGIT) is an immune checkpoint molecule that suppresses CD8+ T‐cell function in cancer. However, the expression profile and functional significance of TIGIT in the immune microenvironment of lung adenocarcinoma (LUAD) remain elusive. Interleukin (IL)‐15 has emerged as a promising candidate for enhancing CD8+ T‐cell mediated tumour eradication. Exploring therapeutic strategies that combine IL‐15 with TIGIT blockade in LUAD is warranted. Methods: We investigated the regulatory network involving coinhibitory TIGIT and CD96, as well as costimulatory CD226 in LUAD using clinical samples. The potential role of TIGIT in regulating the pathogenesis of LUAD was addressed through a murine model with transplanted tumours constructed in Tigit−/− mice. The therapeutic strategy that combines TIGIT blockade with IL‐15 stimulation was verified using a transplanted tumour murine model and a patient‐derived organoid (PDO) model. Results: The frequency of TIGIT+CD8+ T cells was significantly increased in LUAD. Increased TIGIT expression indicated poorer prognosis in LUAD patients. Furthermore, the effector function of TIGIT+CD8+ tumour‐infiltrating lymphocytes (TILs) was impaired in LUAD patients and TIGIT inhibited antitumour immune response of CD8+ TILs in tumour‐bearing mice. Mechanistically, IL‐15 enhanced the effector function of CD8+ TILs but stimulated the expression of TIGIT on CD8+ TILs concomitantly. The application of IL‐15 combined with TIGIT blockade showed additive effects in enhancing the cytotoxicity of CD8+ TILs and thus further increased the antitumour immune response in LUAD. Conclusions: Our findings identified TIGIT as a promising therapeutic target for LUAD. LUAD could benefit more from the combined therapy of IL‐15 stimulation and TIGIT blockade. [ABSTRACT FROM AUTHOR]

Abstract: Using bore gas flux inverse analysis gains coal bed gas flow equation on the basis of coal bed gas occurrence and flow theory, gas radial flow differential equation, using large scale finite element analytical software ANSYS analyse the stress of bore, and gain the stress distributing graph of and further analyze the stress had an impact on coal bed air permeability coefficient and the various rule of gas pressure and coefficient of permeability distribution following stress around bore and gas pressure gradient impacts on gas flow. It has real meaning to gas evacuation, coal mine safety design and coal-bed gas development. [Copyright &y& Elsevier]

Abstract: High-temperature heat-harm of deep mine seriously affects the safety mining of coal mine, so at present the prediction of deep mine''s underground temperature of and underground climate conditions and the treatment of heat- harm have already become the significant safety technology issues of coal mine production. Mine climate was actually measured along with mainly intake and return air routes of Zhangshuanglou coal mine, using drilling hole to measurement temperature and app lying inversion theory of mathematical physics and MATLAB to simulate. The conclusion that the temperature of wall rock of roadways was higher with increasing of depth then to a fixed value while the geothermal gradient was lower with increasing of depth then approached to zero was obtained. Finally the functional expression of the regulating ring of wall rock of laneway was drawn by using the third-order polynomial approximated method, and the deep underground temperature of mining workface 9409, 9109, 7109 and 7505 were predicted, the results of which are accurate, reliable and acceptable. [Copyright &y& Elsevier]

Comprehensive m6A epitranscriptome profiling of primary tumors remains largely uncharted. Here, we profiled the m6A epitranscriptome of 10 non-neoplastic lung (NL) tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating the corresponding transcriptome, proteome and extensive clinical annotations. We identified distinct clusters and genes that were exclusively linked to disease progression through m6A modifications. In comparison with NL tissues, we identified 430 transcripts to be hypo-methylated and 222 to be hyper-methylated in tumors. Among these genes, EML4 emerged as a novel metastatic driver, displaying significant hyper-methylation in tumors. m6A modification promoted the translation of EML4, leading to its widespread overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics through interacting with ARPC1A, enhancing lamellipodia formation, cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. METTL3 small molecule inhibitor markedly diminished both EML4 m6A and protein abundance, and efficiently suppressed lung metastases in vivo.

To investigate the global proteomic profiles of vascular endothelial cells (VECs) in the tumor microenvironment and antiangiogenic therapy for colorectal cancer (CRC), matched pairs of normal (NVECs) and tumor-associated VECs (TVECs) were purified from CRC tissues by laser capture microdissection and subjected to iTRAQ-based quantitative proteomics analysis. Here, 216 differentially expressed proteins (DEPs) were identified and used for bioinformatics analysis. Interestingly, these proteins were implicated in epithelial mesenchymal transition (EMT), ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, angiogenesis and HIF-1 signaling pathway, which may play important roles in CRC angiogenesis. Among these DEPs we found that Tenascin-C (TNC) was upregulated in TVECs of CRC and correlated with CRC multistage carcinogenesis and metastasis. Furthermore, the reduction of tumor-derived TNC could attenuate human umbilical vein endothelial cell (HUVEC) proliferation, migration and tube formation through ITGB3/FAK/Akt signaling pathway. Based on the present work, we provided a large-scale proteomic profiling of VECs in CRC with quantitative information, a certain number of potential antiangiogenic targets and a novel vision in the angiogenesis bio-mechanism of CRC., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)