In silico analysis of HOX-associated transcription factors as potential regulators of oral cancer

Padam, Kanaka Sai Ram; Chakrabarty, Sanjiban; Kabekkodu, Shama Prasada; Paul, Babu Sena; Hunter, Keith D.; Radhakrishnan, Raghu

doi:10.1016/j.oooo.2021.01.002

Cited by 5 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7a). These findings indicate that the role of HOX genes in oral carcinogenesis is tightly modulated and transcriptionally active as previously reported 41 .…”

Section: Hox Gene Deregulation Contributes To the Oral Carcinoma Phen...supporting

confidence: 89%

“…Any alteration in the functional state had consequences leading to phenotypic abnormalities. HOXA10 participated in the transcriptional misregulation in cancer (Table 2) influencing upstream and downstream target interactions as reported previously 41 . HOXB9 was involved in the regulation of the BTG (B-cell translocation gene 1-4) family of proteins which functions in the cell cycle mediated events during cancer progression 42 and was also noted to function as an angiogenic switch along with HOXB7 (Fig.…”

Section: Hox Gene Expression In Oral Cancer Cell Linessupporting

confidence: 65%

See 1 more Smart Citation

Identification of HOX signatures contributing to oral cancer phenotype

Padam

Morgan

Hunter

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

The role of evolutionarily conserved homeobox-containing HOX genes as transcriptional regulators in the developmental specification of organisms is well known. The contribution of HOX genes involvement in oral cancer phenotype has yet to be fully ascertained. TCGA-HNSC HTSeq-counts and clinical data were retrieved from the GDC portal for oral cavity neoplasms. GEO datasets (GSE72627, GSE30784, GSE37991) were accessed and analyzed using GEO2R. Differential HOX gene expression was profiled using the DESeq2 R package with a log2 fold change cut-off (− 1 and + 1) and Benjamini–Hochberg p-adjusted value at ≤ 0.01. Gene set over-representation analysis and semantic analysis associated with the disease ontology was performed using the ClusterProfiler R package, and pathway over-representation analysis was performed using IMPaLa. HOX protein interaction network was constructed using the Pathfind R package. HOX phenotype associations were performed using Mammalian Phenotype Ontology, Human Phenotype Ontology, PhenGenI associations, Jensen tissues, and OMIM entries. Drug connectivity mapping was carried out with Dr. Insight R package. HOXA2 was upregulated in oral dysplasia but silenced during tumor progression. Loss of HOXB2 expression was consistent in the potentially malignant oral lesions as well as in the primary tumor. HOXA7, HOXA10, HOXB7, HOXC6, HOXC10, HOXD10, and HOXD11 were consistently upregulated from premalignancy to malignancy and were notably associated with risk factors. Overrepresentation analysis suggested HOXA10 was involved in the transcriptional misregulation contributing to the oral cancer phenotype. HOX genes subnetwork analysis showed crucial interactions with cell cycle regulators, growth responsive elements, and proto-oncogenes. Phenotype associations specific to the oral region involving HOX genes provide intrinsic cues to tumor development. The 5′ HOX genes were aberrantly upregulated during oral carcinogenesis reflecting their posterior prevalence.

show abstract

“…7a). These findings indicate that the role of HOX genes in oral carcinogenesis is tightly modulated and transcriptionally active as previously reported 41 .…”

Section: Hox Gene Deregulation Contributes To the Oral Carcinoma Phen...supporting

confidence: 89%

Section: Hox Gene Expression In Oral Cancer Cell Linessupporting

confidence: 65%

Identification of HOX signatures contributing to oral cancer phenotype

Padam

Morgan

Hunter

et al. 2022

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Any alteration in the functional state had pathological consequences leading to phenotypic abnormalities. HOXA10 participated in the transcriptional misregulation in cancer (Table 2) in uencing upstream and downstream target interactions as reported previously (Padam et al 2021). HOXB9 is involved in the regulation of the btg family of proteins whose deregulation has implicit biological consequences during cancer progression (Yuniati et al 2019) and was also noted to function as an angiogenic switch along with HOXB7 (Fig.…”

Section: Hox Genes As Developmental Cues In Oral Carcinogenesissupporting

confidence: 62%

Identification of HOX Signatures Contributing to Oral Cancer Phenotype

Padam

Morgan

Hunter

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Purpose: Evolutionarily conserved homeobox-containing HOX genes as transcriptional regulators in the developmental specification of organisms is well known. The contribution of HOX genes involvement in oral cancer phenotype has yet to be fully ascertained.Methods: GEO datasets (GSE72627, GSE30784, GSE37991) were accessed and analyzed using GEO2R. TCGA-HNSC HTSeq-counts and clinical data were retrieved from the GDC portal for oral cavity neoplasms. Differential HOX gene expression was profiled using the DESeq2 R package with a log2 fold change cut-off (-1 and +1) and Benjamini-Hochberg p-adjusted value at <0.01. Gene set over-representation analysis and semantic analysis associated with the disease ontology were performed using ClusterProfiler R package and pathway over-representation analysis was performed using IMPaLa. HOX protein interaction network was constructed using the Pathfind R package. HOX phenotype associations were performed using Mammalian Phenotype Ontology, Human Phenotype Ontology, PhenGenI associations, Jensen tissues, and OMIM entries. Drug connectivity mapping was carried out with Dr. Insight R Package.Results: HOXB2 and HOXA5 genes were upregulated in oral dysplasia but silenced during tumor progression. Loss of HOXB2 expression was consistent through potentially malignant dysplastic oral lesions (PMOL) to primary tumor formation. HOXA10, HOXB7, HOXC6, HOXC10 and HOXD10 showed consistent upregulation from premalignancy to malignancy and were notably associated with risk factors. Overrepresentation analysis suggested HOXA10 was involved in the transcriptional misregulation leading to oral cancer phenotype. HOX subnetwork analysis showed crucial interactions with cell cycle regulators, growth responsive elements, and proto-oncogenes.Conclusion: Phenotype associations specific to the oral region involving HOX genes provide intrinsic cues to tumor development. The 5’ HOX genes were aberrantly deregulated which reflects their posterior prevalence during oral carcinogenesis.

show abstract

“…29 Transcriptomic studies have identified increased expression of DUSP1, Interleukins, SAT1, OAZ1 and S100P in the saliva of patients having OSCC as compared to healthy controls Important transcription factors associated with various malignant and benign neoplasms have been identified in the field of Oral Pathology, which include SOX9, SOX10, SOX11, NKX 2, NKX3, Snail, Slug, TWIST, HOX to name a few. [28][29] Similarly, miRNA-31 was upregulated, whereas eleven distinct types of miRNAs were also found to be deregulated in saliva of patients having oral premalignant and malignant lesions. 30 Transcriptomics has shown promising results in prognostication of disease and predicting treatment outcome in oncology.…”

Section: Transcriptomicsmentioning

confidence: 98%

Omics’ in oral cancer: A comprehensive review

et al. 2022

View full text Add to dashboard Cite

Health and disease states are dictated or accompanied by corresponding alterations in genes, mRNAs, proteins and metabolites. Over the past few decades, various ‘omic’ technologies have been developed to study the genome, transcriptome, proteome and metabolome respectively. Since oral cancers are one of the leading causes of death globally, much of research work has attempted to study the analytes in cancerous conditions by utilizing the various ‘omic’ modalities. These studies have aimed to understand the pathogenesis of head and neck cancers, aid in their diagnosis, devise new treatment strategies, and improve prognosis. It is imperative for surgeons and pathologists to be in line with the updates pertaining to various ‘omic’ methodologies available for studying the analytes. The present review comprehensively describes the development of various ‘omic’ technologies, including- genomics, transcriptomics, proteomics and metabolomics, while emphasizing their applicability in oral cancers.

show abstract

In silico analysis of HOX-associated transcription factors as potential regulators of oral cancer

Cited by 5 publications

References 50 publications

Identification of HOX signatures contributing to oral cancer phenotype

Identification of HOX signatures contributing to oral cancer phenotype

Identification of HOX Signatures Contributing to Oral Cancer Phenotype

Omics’ in oral cancer: A comprehensive review

Contact Info

Product

Resources

About