BackgroundAlkB homolog 5 (ALKBH5) is a N6-methyladenosine (m6A) demethylase associated with the development, growth, and progression of multiple cancer types. However, the biological role of ALKBH5 has not been investigated in pan-cancer datasets. Therefore, in this study, comprehensive bioinformatics analysis of pan-cancer datasets was performed to determine the mechanisms through which ALKBH5 regulates tumorigenesis.MethodsOnline websites and databases such as NCBI, UCSC, CCLE, HPA, TIMER2, GEPIA2, cBioPortal, UALCAN, STRING, SangerBox, ImmuCellAl, xCell, and GenePattern were used to extract data of ALKBH5 in multiple cancers. The pan-cancer patient datasets were analyzed to determine the relationship between ALKBH5 expression, genetic alterations, methylation status, and tumor immunity. Targetscan, miRWalk, miRDB, miRabel, LncBase databases and Cytoscape tool were used to identify microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) that regulate expression of ALKBH5 and construct the lncRNA-miRNA-ALKBH5 network. In vitro CCK-8, wound healing, Transwell and M2 macrophage infiltration assays as well as in vivo xenograft animal experiments were performed to determine the biological functions of ALKBH5 in glioma cells.ResultsThe pan-cancer analysis showed that ALKBH5 was upregulated in several solid tumors. ALKBH5 expression significantly correlated with the prognosis of cancer patients. Genetic alterations including duplications and deep mutations of the ALKBH5 gene were identified in several cancer types. Alterations in the ALKBH5 gene correlated with tumor prognosis. GO and KEGG enrichment analyses showed that ALKBH5-related genes were enriched in the inflammatory, metabolic, and immune signaling pathways in glioma. ALKBH5 expression correlated with the expression of immune checkpoint (ICP) genes, and influenced sensitivity to immunotherapy. We constructed a lncRNA-miRNA network that regulates ALKBH5 expression in tumor development and progression. In vitro and in vivo experiments showed that ALKBH5 promoted proliferation, migration, and invasion of glioma cells and recruited the M2 macrophage to glioma cells.ConclusionsALKBH5 was overexpressed in multiple cancer types and promoted the development and progression of cancers through several mechanisms including regulation of the tumor-infiltration of immune cells. Our study shows that ALKBH5 is a promising prognostic and immunotherapeutic biomarker in some malignant tumors.
Background The function of collagen triple helix repeat containing 1 (CTHRC1) as an oncogene has been reported in a growing number of publications. Bioinformatics methods represent a beneficial approach to examine the mechanism and function of the CTHRC1 gene in the disease process of cancers from a pan-cancer perspective. Methods In this study, using the online databases UCSC, NCBI, HPA, TIMER2, Oncomine, GEPIA, UALCAN, cBioPortal, COSMIC, MEXPRESS, STRING, CCLE, LinkedOmics, GTEx, TCGA, CGGA, and SangerBox, we focused on the relationship between CTHRC1 and tumorigenesis, progression, methylation, immunity, and prognosis. qPCR was used to detect CTHRC1 expression in glioma tissues and cell lines. Results The pan-cancer analysis showed that CTHRC1 was overexpressed in most tumors, and a significant correlation was observed between CTHRC1 expression and the prognosis of patients with cancer. CTHRC1 genetic alterations occur in diverse tumors and are associated with tumor progression. Levels of CTHRC1 promoter methylation were decreased in most cancer tissues compared with normal tissues. In addition, CTHRC1 coordinated the activity of ICP genes through diverse signal transduction pathways, was also associated with immune cell infiltration and the tumor microenvironment, and potentially represented a promising immunotherapy target. We identified CTHRC1-related genes across cancers using the GEPIA2 tool. The single-gene GO analysis of CTHRC1 across cancers showed that it was involved in some signaling pathways and biological processes, such as the Wnt signaling pathway, cell migration, and positive regulation of protein binding. The expression and function of CTHRC1 were also further verified in glioma tissues and cell lines. Conclusions CTHRC1 is overexpressed in various cancer types and functions as an important oncogene that may promote tumorigenesis and development through different mechanisms. CTHRC1 may represent an important therapeutic target for human cancers.
Non-coding RNAs (ncRNAs) account for the majority of the widespread transcripts of mammalian genomes. They rarely encode proteins and peptides, but their regulatory role is crucial in numerous physiological and pathological processes. The m6A (N6-methyladenosine) modification is one of the most common internal RNA modifications in eukaryotes and is associated with all aspects of RNA metabolism. Accumulating researches have indicated a close association between m6A modification and ncRNAs, and suggested m6A-modified ncRNAs played a crucial role in tumor progression. The correlation between m6A modification and ncRNAs offers a novel perspective for investigating the potential mechanisms of cancer pathological processes, which suggests that both m6A modification and ncRNAs are critical prognostic markers and therapeutic targets in numerous malignancies. In the present report, we summarized the interaction between m6A modification and ncRNA, emphasizing how their interaction regulates pathological processes in cancer.
Our previous studies showed that dysregulation of the long noncoding RNA (lncRNA) HOXA11-AS plays an important role in the development of glioma. However, the molecular mechanism of HOXA11-AS in glioma remains largely unknown. In this study, we explore the molecular mechanisms underlying abnormal expression and biological function of HOXA11-AS for identifying novel therapeutic targets in glioma. The expression of HOXA11-AS, and the relationship between HOXA11-AS and the prognosis of glioma patients were analyzed using databases and glioma samples. Transcriptomics, proteomics, RIP, ChIRP, luciferase, and ChIP assays were used to explore its upstream and downstream targets in glioma. The role of HOXA11-AS in regulating the sensitivity of glioma cells to reactive oxygen species (ROS) was also investigated in vitro and in vivo. We found that HOXA11-AS was significantly upregulated in glioma, and was correlated with the poor prognosis of glioma patients. Ectopic expression of HOXA11-AS promoted the proliferation, migration, and invasion of glioma cells in vitro and in vivo. Mechanistically, HOXA11-AS acted as a molecular sponge for let-7b-5p in the cytoplasm, antagonizing its ability to repress the expression of CTHRC1, which activates the β-catenin/c-Myc pathway. In addition, c-Myc was involved in HOXA11-AS dysregulation via binding to its promoter region to form a self-activating loop. HOXA11-AS, functioned as a scaffold in the nucleus, also recruited transcription factor c-Jun to the Tpl2 promoter, which activates the Tpl2-MEK1/2-ERK1/2 pathway to promote ROS resistance in glioma. Importantly, HOXA11-AS knockdown could sensitize glioma cells to ROS. Above, oncogenic HOXA11-AS upregulates CTHRC1 expression as a ceRNA by adsorbing let-7b-5p, which activates c-Myc to regulate itself transcription. HOXA11-AS knockdown promotes ROS sensitivity in glioma cells by regulating the Tpl2-MEK1/2-ERK1/2 axis, demonstrating that HOXA11-AS may be translated to increase ROS sensitivity therapeutically.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.