Authors : Heth J. Bhatt

Volume/Issue : Volume 9 - 2024, Issue 9 - September

Google Scholar : https://tinyurl.com/yhfht54e

Scribd : https://tinyurl.com/umef8xnk

DOI : https://doi.org/10.5281/zenodo.14357953

Abstract : Zinc Finger Protein 835 (ZNF835) is a protein- coding gene involved in DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding. This gene plays a significant role in the regulation of transcription by RNA polymerase II and is implicated in various cancer-related processes. ZNF835 has been predicted to interact with oncogenes and microRNAs (miRs) associated with tumor growth, suggesting its potential role as an oncogene. Notably, specific SNPs in African American males may target ZNF835, increasing their predisposition to certain cancers. This research paper explores ZNF835’s functional roles, its potential as an oncogene through various molecular pathways, its interactions with transcription factors and miRs, and the application of immunohistochemistry (IHC) and artificial intelligence (AI) in predicting and diagnosing cancer.

References :

1. Alliance of Genome Resources. Version 7.3.0. Alliance of Genome Resources, www.alliancegenome.org/gene/HGNC:34332#summary. Accessed 31 Aug. 2024.This website gave me relevant information about the gene, including the orthology, pathways, phenotypes, disease associations, alleles, variants, expression, and molecular interactions. The information pathogenicity portion of my paper comes from this website.
2. AlphaFold Protein Structure Database. AlphaFold Protein Structure Database, Google DeepMind, EMBL-EBI, alphafold.ebi.ac.uk/entry/Q9Y2P0. Accessed 31 Aug. 2024. "AlphaFold is an AI system developed by Google DeepMind that predicts a protein's 3D structure from its amino acid sequence. It regularly achieves accuracy competitive with experiment." I used the database to learn more about structure, pathogenicity, predicted aligned error, and ZNF835's AlphaMissense pathogenicity heatmap.                       
3. Gene Cards the Human Gene Database. Version 5.21.0. GeneCards the Human Gene Database, Life Map Sciences, Weizman Institute of Science, 1996, www.genecards.org/cgi-bin/carddisp.pl?gene=ZNF835#expression. Accessed 31 Aug. 2024. "GeneCards is a searchable, integrative database that provides comprehensive, user-friendly information on all annotated and predicted human genes. The knowledgebase automatically integrates gene-centric data from ~150 web sources, including genomic, transcriptomic, proteomic, genetic, clinical and functional information." I used the browser for information ZNF835's genomics, expression, tra nscripts and variants.                      
4. Heit JA, Armasu SM, McCauley BM, Kullo IJ, Sicotte H, Pathak J, Chute CG, Gottesman O, Bottinger EP, Denny JC, Roden DM, Li R, Ritchie MD, de Andrade M. Identification of unique venous thromboembolism-susceptibility variants in African-Americans. Thromb Haemost. 2017 Apr 3;117(4):758-768. doi: 10.1160/TH16-08-0652. Epub 2017 Feb 16. PMID: 28203683; PMCID: PMC5831339. I used this work to further look into the phenotypic results of the oncogenic expression of the ZNF835 gene, and to research more about the SNP present in the African American male genome, potentially causing cancer. The Human Protein Atlas. The Human Protein Atlas, ELIXIR, www.proteinatlas.org/ENSG00000127903-ZNF835/tissue. "The Human Protein Atlas is a Swedish-based program initiated in 2003 with the aim to map all the human proteins in cells, tissues, and organs using an integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics, and systems biology." I used the database for tissue slices, and images of expression of the gene for use in datasets to feed the artificial intelligence model in its work in histology and immunohistochemistry (IHC).                               
5. Jovov B, Araujo-Perez F, Sigel CS, Stratford JK, McCoy AN, Yeh JJ, Keku T. Differential gene expression between African American and European American colorectal cancer patients. PLoS One. 2012;7(1):e30168. doi: 10.1371/journal.pone.0030168. Epub 2012 Jan 19. PMID: 22276153; PMCID: PMC3261881. I used this paper to learn more about the oncogene potential about ZNF835, as well as the specific SNP that could be linked to cause cancerous tumors within the genome specific to African American males. This research paper was written from professors at the University of North Carolina at Chapel Hill.                                                      
6. Kent, W. James, et al. UCSC Genome Browser. 6th ed. UCSC Genome Browser on Human, University of California, Santa Cruz, 12 June 2002, genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&lastVirtModeType=default&lastVirtModeExtraState=&virtModeType=default&virtMode=0&nonVirtPosition=&position=chr19%3A43687335%2D58354334&hgsid=2341007860_4bdzR5kUQEuNa6aaCTNdO0OBQ1Cg. Accessed 31 Aug. 2024. The browser was created by scientists and researchers from the University of California, Santa Cruz. I used the browser to utilize the genome sequences, and annotations about gene predictions, expression data, and comparative genomics data. Messeguer, Xavier, et al. Alggen. Version 3.0.2. ALGGEN, 18 Feb. 2002, alggen.lsi.upc.es/cgi-bin/promo_v3/promo/promoinit.cgi?dirDB=TF_8.3. Accessed 31 Aug. 2024. This website provided me information about all the transcription factors of ZNF835. The site "is a collaborative research project between Dr. M.M. Albà and D. Farré at the Evolutionary Genomics Group (Research Unit on Biomedical Informatics, Universitat Pompeu Fabra) and D. García, R. Escudero, O. Nuñez,
7. J. Martínez and Dr. X. Messeguer of the Universitat Politècnica de Catalunya." Tables, graphs, and charts of potential transcription factors of the gene ZNF835. Dire Dcode, National Library of Medicine, dire.dcode.org/index.php?id=0711241211935093&finished=1. Accessed 31 Aug. 2024. This website, created by Ivan Ovcharenko of the National Library of Medicine, provided specific information in the form of tables including regulatory elements, and candidate transcription factors of the research gene ZNF835.                                     
8. TargetScanHuman Prediction of microRNA Targets. Version 8.0.0. TargetScanHuman, Sept. 2021, www.targetscan.org/cgi-bin/vert_80/view_gene.cgi?rs=ENST00000537055.2&taxid=9606&members=&subset=1&showcnc=1&shownc=1&shownc_nc=0&showncf1=0#let-7-5p/miR-98-5p. Accessed 31 Aug. 2024. "TargetScan predicts biological targets of miRNAs by searching for the presence of conserved 8mer, 7mer, and 6mer sites that match the seed region of each miRNA. As options, predictions with only poorly conserved sites and predictions with nonconserved miRNAs are also provided." I had used this site for information and research about the conservation sites for miRNA families in ZNF835.