MicroRNA-375 inhibits glioma cell proliferation and migration by downregulating RWDD3 in vitro chen-XIng JI, yang-hua Fan, Fan Xu, shI-gang lv, MIn-hua ye, MIao-JIng Wu, XIn-gen Zhu and leI Wu

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MicroRNA-375 inhibits glioma cell proliferation and migration by downregulating RWDD3 in vitro chen-XIng JI, yang-hua Fan, Fan Xu, shI-gang lv, MIn-hua ye, MIao-JIng Wu, XIn-gen Zhu and leI Wu This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Background: Transporter associated with antigen processing 1 (TAP1) is a transporter that processes and presents the major histocompatibility complex class I (MHC-I) restricted antigens, including tumor-associated antigens. TAP1 is aberrantly expressed in multiple cancer types, and also involves in tumor immunity. Therefore, the predictive role of TAP1 in cancer development and treatment is expected. Methods: Transcriptomic profiles were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Genetic alteration, protein distribution and interaction information were downloaded from cbioPortal, Human Protein Atlas (HPA) and Compartmentalized Protein-Protein Interaction (ComPPI), respectively. Single-cell analysis was conducted on Tumor Immune Single-cell Hub (TISCH) website. Gene set enrichment analysis (GSEA) was employed to investigate the functioning mechanism of TAP1 by R package “clusterProfiler”. Immune cell infiltration of Pan-cancer was explored by Tumor Immune Estimation Resource (TIMER) 2.0 webtool and visualized by R programming language. Correlation between TAP1 expression and immunotherapy biomarkers was explored using Spearman’s correlation test. Association with immunotherapy responses of TAP1 was investigated using the information of the cancer cohorts with patients received immune checkpoint inhibitors (ICIs). Results: TAP1 expression was elevated in most pan-cancer types and exhibited distinct prognostic value in diverse cancer types. Within tumor tissues, immune cells expressed more TAP1 than malignant cells. TAP1 expression was significantly correlated with immune-related pathways, infiltration of T lymphocytes and immunotherapeutic biomarkers. Cohort validation revealed a significant correlation with immune therapeutic effects and verified the prognostic role of TAP1 in immunotherapy. Western blot assay indicated that TAP1 is upregulated in GBMs compared with adjacent normal brain tissues (NBTs).Conclusion: TAP1 was a robust tumor biomarker, and a novel predictor of clinical prognosis and immunotherapeutic responses in distinct cancer types.

Background: Lysine acetylation is a crucial kind of protein modification and is related to the malignant development of various cancers. But their roles in glioma are still unclear and needed concluded comprehensively. Methods: In this study, we comprehensively analyzed the expression levels of 33 lysine acetylation regulators (LARs) and prognostic roles by using public data, including the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). The prognostic roles of LARs were judged by univariate Cox regression. Consensus clustering was applied to result in three stratified glioma subtypes (LA1, 2, and 3) with different clinical outcomes. We also constructed a risk signature for predicting the overall survival of glioma patients by using least absolute shrinkage and selection operator regression (LASSO regression). Besides, copy number variations (CNVs) and single nucleotide polymorphism (SNP) of LARs were also analyzed in our study. Results: We found the mRNA expression levels of most of LARs were dysregulated in gliomas and associated with the prognosis of glioma patients. The risk signature constructed by 14 LARs presented an independent prognostic role in both the CGGA (HR:1.96, 95%CI:1.33-2.90) and TCGA (HR:1.48, 95%CI:1.08-2.03) datasets and robust predictive effects in the ROC curves with all of area under curves more than 0.800. Moreover, the copy number variations of LARs were also significantly related to the prognosis of glioma patients, in which HDAC1 (1p) was one of the oncogenes lost in 1p/19q codeletion events, while SIRT2 (19q) and EP300 (22q) may act as tumor suppressors in gliomas with 19q or 22q deletions, respectively. Conclusion: LARs are potential biomarkers for the malignant progression of gliomas, and our results could be useful for predicting the OS of glioma patients and provide some clues in searching the functions of LARs in glioma progression. Keywords: glioma, lysine acetylation regulator, epigenetic, prognostic signature, biomarker.