scholarly journals Comprehensive Analyses of the Expression, Genetic Alteration, Prognosis Significance, and Interaction Networks of m6A Regulators Across Human Cancers

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiujuan Shi ◽  
Jieping Zhang ◽  
Yuxiong Jiang ◽  
Chen Zhang ◽  
Xiaoli Luo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Genetic Alteration ◽  
Multiple Cancer ◽  
Aberrant Expression ◽  
Rna Methylation ◽  
Oncogenic Pathways ◽  
Cancer Types ◽  
Upstream Regulators ◽  
Shed Light

Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein–protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators–potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators’ roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.

scholarly journals Targeting SRC Family Kinases in Mesothelioma: Time to Upgrade

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1866
Author(s):  
Paola Indovina ◽  
Iris Maria Forte ◽  
Francesca Pentimalli ◽  
Antonio Giordano
Keyword(s):  
Receptor Tyrosine Kinase ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Current Treatment ◽  
Src Family Kinases ◽  
Oncogenic Pathways ◽  
History Of ◽  
Cancer Types ◽  
Preclinical And Clinical Studies ◽  
Lost In Translation

Malignant mesothelioma (MM) is a deadly tumor mainly caused by exposure to asbestos. Unfortunately, no current treatment is able to change significantly the natural history of the disease, which has a poor prognosis in the majority of patients. The non-receptor tyrosine kinase SRC and other SRC family kinase (SFK) members are frequently hyperactivated in many cancer types, including MM. Several works have indeed suggested that SFKs underlie MM cell proliferation, survival, motility, and invasion, overall affecting multiple oncogenic pathways. Consistently, SFK inhibitors effectively counteracted MM cancerous features at the preclinical level. Dasatinib, a multi-kinase inhibitor targeting SFKs, was also assessed in clinical trials either as second-line treatment for patients with unresectable MM or, more recently, as a neoadjuvant agent in patients with resectable MM. Here, we provide an overview of the molecular mechanisms implicating SFKs in MM progression and discuss possible strategies for a more successful clinical application of SFK inhibitors. Our aim is to stimulate discussion and further consideration of these agents in better designed preclinical and clinical studies to make the most of another class of powerful antitumoral drugs, which too often are lost in translation when applied to MM.

scholarly journals LINC00152 Acts as a Potential Marker in Gliomas and Promotes Tumor Proliferation and Invasion Through The LINC00152/miR-107/RAB10 Axis

2021 ◽  
Author(s):  
qing liu ◽  
gang peng ◽  
Jun Su ◽  
zeyou wang ◽  
songhua xiao
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Experimental Studies ◽  
Pivotal Role ◽  
Aberrant Expression ◽  
Potential Marker ◽  
Induced Apoptosis ◽  
Proliferation And Invasion

Abstract Aberrant expression of long noncoding RNAs plays a pivotal role in tumorigenesis. Recently, several studies have showed that the LINC00152 gene is upregulated in a variety of tumors and plays an oncogene role; however, its underlying molecular mechanisms in glioblastoma remain unclear. In this study, we found that LINC00152 was upregulated in gliomas and its expression was significantly associated with high tumor aggressiveness and poor outcomes for glioma patients through bioinformatics analysis. Functionally, the knockdown of LINC00152 not only inhibited malignant behaviors of glioma, such as proliferation and invasion of glioma cells and induced apoptosis in vitro but also suppressed tumorigenesis in vivo. Mechanistically, results of the bioinformatics analysis and experimental studies confirmed that LINC00152 and RAB10 as the targets of miR-107, and LINC00152 might act as a sponge for miR-107 to regulate the expression of RAB10 in glioblastoma. Additionally, silencing miR-107 reversed the effects induced by LINC00152 knockdown on glioblastoma cells both in vitro and in vivo. Taken together, our data suggested that LINC00152 is a candidate prognostic marker of glioma, and that the LINC00152/MIR-107/RAB10 axis plays a pivotal role in regulation of the glioma malignancy, and therefore, targeting the axis might be an effective therapeutic strategy to treat glioma.

scholarly journals Genetic alteration and clinical significance of SUMOylation regulators in multiple cancer types

2020 ◽  
Vol 11 (23) ◽  
pp. 6823-6833
Author(s):  
Guangzhen Wu ◽  
Yingkun Xu ◽  
Ningke Ruan ◽  
Jianyi Li ◽  
Qingyang Lv ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Genetic Alteration ◽  
Multiple Cancer ◽  
Cancer Types

scholarly journals Identifying cancer type specific oncogenes and tumor suppressors using limited size data

2016 ◽  
Vol 14 (06) ◽  
pp. 1650031 ◽  
Author(s):  
Ana B. Pavel ◽  
Cristian I. Vasile
Keyword(s):  
Tumor Suppressors ◽  
Molecular Mechanisms ◽  
Lung Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Driver Mutations ◽  
Cancer Type ◽  
Multiple Cancer ◽  
Driver Genes ◽  
Cancer Subtypes ◽  
Cancer Types

Cancer is a complex and heterogeneous genetic disease. Different mutations and dysregulated molecular mechanisms alter the pathways that lead to cell proliferation. In this paper, we explore a method which classifies genes into oncogenes (ONGs) and tumor suppressors. We optimize this method to identify specific (ONGs) and tumor suppressors for breast cancer, lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and colon adenocarcinoma (COAD), using data from the cancer genome atlas (TCGA). A set of genes were previously classified as ONGs and tumor suppressors across multiple cancer types (Science 2013). Each gene was assigned an ONG score and a tumor suppressor score based on the frequency of its driver mutations across all variants from the catalogue of somatic mutations in cancer (COSMIC). We evaluate and optimize this approach within different cancer types from TCGA. We are able to determine known driver genes for each of the four cancer types. After establishing the baseline parameters for each cancer type, we identify new driver genes for each cancer type, and the molecular pathways that are highly affected by them. Our methodology is general and can be applied to different cancer subtypes to identify specific driver genes and improve personalized therapy.

scholarly journals Small ring has big potential: insights into extrachromosomal DNA in cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yihao Wang ◽  
Rui Huang ◽  
Guopei Zheng ◽  
Jianfeng Shen
Keyword(s):  
Molecular Mechanisms ◽  
Small Ring ◽  
Extrachromosomal Dna ◽  
Multiple Cancer ◽  
Normal Tissues ◽  
Oncogene Activation ◽  
Technical Advances ◽  
Cancer Types ◽  
Underlying Mechanisms

AbstractRecent technical advances have led to the discovery of novel functions of extrachromosomal DNA (ecDNA) in multiple cancer types. Studies have revealed that cancer-associated ecDNA shows a unique circular shape and contains oncogenes that are more frequently amplified than that in linear chromatin DNA. Importantly, the ecDNA-mediated amplification of oncogenes was frequently found in most cancers but rare in normal tissues. Multiple reports have shown that ecDNA has a profound impact on oncogene activation, genomic instability, drug sensitivity, tumor heterogeneity and tumor immunology, therefore may offer the potential for cancer diagnosis and therapeutics. Nevertheless, the underlying mechanisms and future applications of ecDNA remain to be determined. In this review, we summarize the basic concepts, biological functions and molecular mechanisms of ecDNA. We also provide novel insights into the fundamental role of ecDNA in cancer.

scholarly journals Insights Into the Function and Clinical Application of HDAC5 in Cancer Management

2021 ◽  
Vol 11 ◽  
Author(s):  
Jun Yang ◽  
Chaoju Gong ◽  
Qinjian Ke ◽  
Zejun Fang ◽  
Xiaowen Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Regulatory Mechanisms ◽  
Biological Functions ◽  
Multiple Cancer ◽  
Aberrant Expression ◽  
Cancer Management ◽  
Cancer Types ◽  
Proliferation And Invasion

Histone deacetylase 5 (HDAC5) is a class II HDAC. Aberrant expression of HDAC5 has been observed in multiple cancer types, and its functions in cell proliferation and invasion, the immune response, and maintenance of stemness have been widely studied. HDAC5 is considered as a reliable therapeutic target for anticancer drugs. In light of recent findings regarding the role of epigenetic reprogramming in tumorigenesis, in this review, we provide an overview of the expression, biological functions, regulatory mechanisms, and clinical significance of HDAC5 in cancer.

scholarly journals Comprehensive Analysis of Expression Regulation for RNA m6A Regulators With Clinical Significance in Human Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaonan Liu ◽  
Pei Wang ◽  
Xufei Teng ◽  
Zhang Zhang ◽  
Shuhui Song
Keyword(s):  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Critical Role ◽  
Expression Regulation ◽  
The Cancer Genome Atlas ◽  
Aberrant Expression ◽  
Human Cancers ◽  
Cancer Types ◽  
Pan Cancer

BackgroundN6-methyladenosine (m6A), the most abundant chemical modification on eukaryotic messenger RNA (mRNA), is modulated by three class of regulators namely “writers,” “erasers,” and “readers.” Increasing studies have shown that aberrant expression of m6A regulators plays broad roles in tumorigenesis and progression. However, it is largely unknown regarding the expression regulation for RNA m6A regulators in human cancers.ResultsHere we characterized the expression profiles of RNA m6A regulators in 13 cancer types with The Cancer Genome Atlas (TCGA) data. We showed that METTL14, FTO, and ALKBH5 were down-regulated in most cancers, whereas YTHDF1 and IGF2BP3 were up-regulated in 12 cancer types except for thyroid carcinoma (THCA). Survival analysis further revealed that low expression of several m6A regulators displayed longer overall survival times. Then, we analyzed microRNA (miRNA)-regulated and DNA methylation-regulated expression changes of m6A regulators in pan-cancer. In total, we identified 158 miRNAs and 58 DNA methylation probes (DMPs) involved in expression regulation for RNA m6A regulators. Furthermore, we assessed the survival significance of those regulatory pairs. Among them, 10 miRNAs and 7 DMPs may promote cancer initiation and progression; conversely, 3 miRNA/mRNA pairs in kidney renal clear cell carcinoma (KIRC) may exert tumor-suppressor function. These findings are indicative of their potential prognostic values. Finally, we validated two of those miRNA/mRNA pairs (hsa-miR-1307-3p/METTL14 and hsa-miR-204-5p/IGF2BP3) that could serve a critical role for potential clinical application in KIRC patients.ConclusionsOur findings highlighted the importance of upstream regulation (miRNA and DNA methylation) governing m6A regulators’ expression in pan-cancer. As a result, we identified several informative regulatory pairs for prognostic stratification. Thus, our study provides new insights into molecular mechanisms of m6A modification in human cancers.

scholarly journals Bioinformatics Analysis of Differentially Expressed Rhythm Genes in Liver Hepatocellular Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Huaifeng Liu ◽  
Yu Gao ◽  
Shangshang Hu ◽  
Zhengran Fan ◽  
Xianggang Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Rate ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Aberrant Expression ◽  
Expression Levels ◽  
Incidence And Mortality ◽  
Liver Hepatocellular Carcinoma

Liver Hepatocellular Carcinoma (LIHC), a malignant tumor with high incidence and mortality, is one of the most common cancers in the world. Multiple studies have found that the aberrant expression of rhythm genes is closely related to the occurrence of LIHC. This study aimed to use bioinformatics analysis to identify differentially expressed rhythm genes (DERGs) in LIHC. A total of 563 DERGs were found in LIHC, including 265 downregulated genes and 298 upregulated genes. KEGG pathway enrichment and GO analyses showed that DERGs were significantly enriched in rhythmic and metabolic processes. Survival analysis revealed that high expression levels of CNK1D, CSNK1E, and NPAS2 were significantly associated with the low survival rate in LIHC patients. Through cell experiment verification, the mRNA expression levels of CSNK1D, CSNK1E, and NPAS2 were found to be strongly upregulated, which was consistent with the bioinformatics analysis of LIHC patient samples. A total of 23 nodes and 135 edges were involved in the protein–protein interaction network of CSNK1D, CSNK1E, and NPAS2 genes. Clinical correlation analyses revealed that CSNK1D, CSNK1E, and NPAS2 expression levels were high-risk factors and independently connected with the overall survival rate in LIHC patients. In conclusion, the identification of these DERGs contributes to the exploration of the molecular mechanisms of LIHC occurrence and development and may be used as diagnostic and prognostic biomarkers and molecular targets for chronotherapy in LIHC patients in the future.

scholarly journals Multi-Approach Bioinformatics Analysis of Curated Omics Data Provides a Gene Expression Panorama for Multiple Cancer Types

2020 ◽  
Vol 11 ◽  
Author(s):  
Bruno César Feltes ◽  
Joice de Faria Poloni ◽  
Itamar José Guimarães Nunes ◽  
Sara Socorro Faria ◽  
Marcio Dorn
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Gene Expression Omnibus ◽  
Rna Seq ◽  
Multiple Cancer ◽  
Heterogeneous Nature ◽  
Cancer Types ◽  
Learning Analysis ◽  
Overall Survival Analysis

Studies describing the expression patterns and biomarkers for the tumoral process increase in number every year. The availability of new datasets, although essential, also creates a confusing landscape where common or critical mechanisms are obscured amidst the divergent and heterogeneous nature of such results. In this work, we manually curated the Gene Expression Omnibus using rigorous filtering criteria to select the most homogeneous and highest quality microarray and RNA-seq datasets from multiple types of cancer. By applying systems biology approaches, combined with machine learning analysis, we investigated possible frequently deregulated molecular mechanisms underlying the tumoral process. Our multi-approach analysis of 99 curated datasets, composed of 5,406 samples, revealed 47 differentially expressed genes in all analyzed cancer types, which were all in agreement with the validation using TCGA data. Results suggest that the tumoral process is more related to the overexpression of core deregulated machinery than the underexpression of a given gene set. Additionally, we identified gene expression similarities between different cancer types not described before and performed an overall survival analysis using 20 cancer types. Finally, we were able to suggest a core regulatory mechanism that could be frequently deregulated.

scholarly journals LINC00152 Acts as a Potential Marker in Gliomas and Promotes Tumor Proliferation and Invasion Through the LINC00152/miR-107/RAB10 Axis

2021 ◽  
Author(s):  
Qing Liu ◽  
gang peng ◽  
jun su ◽  
songhua xiao
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Flow Cytometric Analysis ◽  
Pivotal Role ◽  
Cell Counting ◽  
Glioblastoma Cells ◽  
Aberrant Expression ◽  
Proliferation And Invasion

Abstract Purpose: Aberrant expression of long noncoding RNAs plays a pivotal role in tumorigenesis. Recently, several studies have showed that the LINC00152 gene is upregulated in a variety of tumors and plays an oncogene role; however, its underlying molecular mechanisms in glioblastoma remain unclear. In this study,we prepare to investigate the biological role and underlying molecular mechanisms of LINC00152 in glioblastoma cells. Methods: Bioinformatics analysis to identify LINC00152 expression, Cell Counting kit-8 assay and Colony formation assay were used to evaluate proliferation, Flow cytometric analysis was used to evaluate apoptosis, Cell Matrigel invasion assay and Wound healing assay was used to evaluate invasion, Western blot analysis to check protein expression level, Mouse xenograft models was used to check cell proliferation in vivo.Results: In this study, we found that LINC00152 was upregulated in gliomas and its expression was significantly associated with high tumor aggressiveness and poor outcomes for glioma patients. Functionally, the knockdown of LINC00152 not only inhibited malignant behaviors of glioma, such as proliferation and invasion of glioma cells and induced apoptosis in vitro but also suppressed tumorigenesis in vivo. Mechanistically, results of the bioinformatics analysis and experimental studies confirmed that LINC00152 and RAB10 as the targets of miR-107, and LINC00152 might act as a sponge for miR-107 to regulate the expression of RAB10 in glioblastoma. Additionally, silencing miR-107 reversed the effects induced by LINC00152 knockdown on glioblastoma cells both in vitro and in vivo. Conclusion: Our data suggested that LINC00152 is a candidate prognostic marker of glioma, and that the LINC00152/MIR-107/RAB10 axis plays a pivotal role in regulation of the glioma malignancy, and therefore, targeting the axis might be an effective therapeutic strategy to treat glioma.

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