Cohesin subunit RAD21: From biology to disease

Cheng, Haizi; Zhang, Nenggang; Pati, Debananda

doi:10.1016/j.gene.2020.144966

Cited by 82 publications

(68 citation statements)

References 190 publications

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“…Cohesin is among the most commonly mutated protein complexes in cancer (Waldman 2020), and somatic mutations and amplification of RAD21 have been reported in human tumors (Cheng, et al 2020). The N-terminus of the corresponding sequences (321–346 in RAD21) contains part of the nuclear localization signal: 317–339 in RAD21 (Cheng, et al 2020) and 253–261 in TriH. We expect that this TriH domain enters nuclei and interacts with cohesin kleisin to affect cohesin action.…”

Section: Resultsmentioning

confidence: 99%

“…Cohesin is among the most commonly mutated protein complexes in cancer (Waldman 2020), and somatic mutations and amplification of RAD21 have been reported in human tumors (Cheng, et al 2020). The N-terminus of the corresponding sequences (321-346 in RAD21) contains part of the nuclear localization signal: 317-339 in RAD21 (Cheng, et al 2020) and 253-261 322 . CC-BY 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Section: Novel Virulence Factor/oncoprotein Candidatesmentioning

confidence: 99%

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Genome-wide association study of gastric cancer- and duodenal ulcer-derivedHelicobacter pyloristrains reveals discriminatory amino acid differences and novel oncoprotein candidates

Tuan

Yahara

Dung

et al. 2021

Preprint

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Genome-wide association studies (GWASs) can reveal genetic variations associated with a phenotype in the absence of any hypothesis of candidate genes. The problem of false-positive sites linked with the responsible site might be bypassed in bacteria with a high homologous recombination rate, such as Helicobacter pylori, which causes gastric cancer (GC). We conducted a GWAS followed by regression-based prediction of GC and duodenal ulcer H. pylori strains. We identified 14 single nucleotide polymorphisms (11 amino acid changes) that, combined, allowed effective disease discrimination. They were often informative of the underlying molecular mechanisms, such as electric charge alteration at the ligand-binding pocket, alteration in subunit interaction, and mode-switching of DNA methylation. We also identified three novel virulence factors/oncoprotein candidates. These results provide both defined targets for further informatic and experimental analyses to gain insights into GC pathogenesis and a basis for identifying a set of biomarkers for application in clinical settings.

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Section: Resultsmentioning

confidence: 99%

“…Cohesin is among the most commonly mutated protein complexes in cancer (Waldman 2020), and somatic mutations and amplification of RAD21 have been reported in human tumors (Cheng, et al 2020). The N-terminus of the corresponding sequences (321-346 in RAD21) contains part of the nuclear localization signal: 317-339 in RAD21 (Cheng, et al 2020) and 253-261 322 . CC-BY 4.0 International license made available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Section: Novel Virulence Factor/oncoprotein Candidatesmentioning

confidence: 99%

Genome-wide association study of gastric cancer- and duodenal ulcer-derivedHelicobacter pyloristrains reveals discriminatory amino acid differences and novel oncoprotein candidates

Tuan

Yahara

Dung

et al. 2021

Preprint

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“…RAD21 is involved in the regulation of the normal cell cycle, DNA, DSB repair, and apoptosis pathways. In addition, the germline heterozygous or homozygous missense mutations of RAD21 are related to human genetic diseases [ 23 ]. XPO1 is an export receptor responsible for the nuclear-cytoplasmic transport of hundreds of proteins and various RNAs.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling and Biofunction Analysis of HepG2 Cells Targeted by Crocetin

Wen

Zhu

et al. 2021

Mediators of Inflammation

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Crocetin is a carotenoid extracted from Gardenia jasminoides, one of the most popular traditional Chinese medicines, which has been used in the prevention and treatment of various diseases. The present study is aimed at clarifying the effect of crocetin on gene expression profiling of HepG2 cells by RNA-sequence assay and further investigating the molecular mechanism underlying the multiple biofunctions of crocetin based on bioinformatics analysis and molecular evidence. Among a total 23K differential genes identified, crocetin treatment upregulated the signals of 491 genes (2.14% of total gene probes) and downregulated the signals of 283 genes (1.24% of total gene probes) by ≥2-fold. The Gene Ontology analysis enriched these genes mainly on cell proliferation and apoptosis (BRD4 and DAXX); lipid formation (EHMT2); cell response to growth factor stimulation (CYP24A1 and GCNT2); and growth factor binding (ABCB1 and ABCG1), metabolism, and signal transduction processes. The KEGG pathway analysis revealed that crocetin has the potential to regulate transcriptional misregulation, ABC transporters, bile secretion, alcoholism, systemic lupus erythematosus (SLE), and other pathways, of which SLE was the most significantly disturbed pathway. The PPI network was constructed by using the STRING online protein interaction database and Cytoscape software, and 21 core proteins were obtained. RT-qPCR datasets serve as the solid evidence that verified the accuracy of transcriptome sequencing results with the same change trend. This study provides first-hand data for comprehensively understanding crocetin targeting on hepatic metabolism and its multiple biofunctions.

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“…Among the genes involved in the pathway of cancer, lncRNA activated by APC can inhibit the occurrence of colorectal cancer by reducing the production of exosomes [34]; LINC01638 activated by SP1 can promote the proliferation and migration of gastric cancer cells by regulating epithelial-mesenchymal transition [35]; as a target of miR-379, CHUK inhibition induced by miR-379 can prevent the growth of NSCLC tumors [36]; abnormality in the Fas signaling pathway involved by MAPK8 can increase the risk of gastric cancer [37]; activated Rho/ROCK1 signaling pathway can worsen breast cancer [38]. Among the genes involved in the cell cycle, the RAD21 protein complex composed of genes such as SMC and SMC1A participates in the aggregation of sister chromatids [39]. Similarly, STAG1/STAG2 is also part of the adhesion protein complex, which participates in the adhesion of sister chromatids [40].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive biological information analysis of PTEN gene in pan-cancer

Zhang¹,

Zhou²,

Yang³

et al. 2021

Preprint

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Background PTEN is a multifunctional tumor suppressor gene mutating at high frequency in a variety of cancers. However, its expression in pan-cancer, correlated genes, survival prognosis, and regulatory pathways are not completely described. Here, we aimed to conduct a comprehensive analysis from the above perspectives in order to provide reference for clinical application. Methods we studied the expression levels in cancers by using data from TCGA and GTEx database. Obtain expression box plot from UALCAN database. Perform mutation analysis on the cBioportal website. Obtain correlation genes on the GEPIA website. Construct protein network and perform KEGG and GO enrichment analysis on the STRING database. Perform prognostic analysis on the Kaplan-Meier Plotter website. We also performed transcription factor prediction on the PROMO database and performed RNA-RNA association and RNA-protein interaction on the RNAup Web server and RPISEq. The gene 3D structure, protein sequence and conserved domain were obtained in NCBI respectively. Results PTEN was underexpressed in all cancers we studied. It was closely related to the clinical stage of tumors, suggesting PTEN may involved in cancer development and progression. The mutations of PTEN were present in a variety of cancers, most of which were truncation mutations and missense mutations. Among cancers (KIRC, LUAD, THYM, UCEC, Gastric Cancer, Liver Cancer, Lung Cancer, Breast Cancer), patients with low expression of PTEN had a shorter OS time and poorer OS prognosis. The low expression of PTEN can cause the deterioration of RFS in certain cancers (TGCT, UCEC, LIHC, LUAD, THCA), suggesting that the expression of PTEN was related to the clinical prognosis. Our study identified genes correlated with PTEN and performed GO enrichment analysis on 100 PTEN-related genes obtained from the GEPIA website. Conclusions The understanding of PTEN gene and the in-depth exploration of its related regulatory pathways may provide insight for the discovery of tumor-specific biomarkers and clinical potential therapeutic targets.

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Cohesin subunit RAD21: From biology to disease

Cited by 82 publications

References 190 publications

Genome-wide association study of gastric cancer- and duodenal ulcer-derivedHelicobacter pyloristrains reveals discriminatory amino acid differences and novel oncoprotein candidates

Genome-wide association study of gastric cancer- and duodenal ulcer-derivedHelicobacter pyloristrains reveals discriminatory amino acid differences and novel oncoprotein candidates

Gene Expression Profiling and Biofunction Analysis of HepG2 Cells Targeted by Crocetin

Comprehensive biological information analysis of PTEN gene in pan-cancer

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