Epigenomic integrative analysis pinpoint master regulator transcription factors associated with tumorigenesis in squamous cell carcinoma of oral tongue

Okano, Larissa Miyuki; Fonseca, Lívia Maria Maciel da; Erthal, Isabela Dias; Malta, Tathiane Maistro

doi:10.1590/1678-4685-GMB-2022-0358

Larissa Miyuki Okano

data curation

investigation

methodology

ELMER analysis

visualization

writing-original draft

writing-review and editing

data generation

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brazil.

* These authors contributed equally to this study

https://orcid.org/0000-0002-7940-9671

Lívia Maria Maciel da Fonseca

investigation

data processing

analysis

visualization

writing-review and editing

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, SP, Brazil.

* These authors contributed equally to this study

https://orcid.org/0000-0003-1551-7996

Isabela Dias Erthal

investigation

methodology

ELMER analysis

Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brazil.

Tathiane Maistro Malta

project administration

conceptualization

formal analysis

supervision

visualization

writing-review and editing

Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto, SP, Brazil.

https://orcid.org/0000-0003-1129-5791

*
These authors contributed equally to this study

Send correspondence to Tathiane Maistro Malta. Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Av. do Café, s/n, Vila Monte Alegre, 14040-900 Ribeirão Preto, SP, Brazil. E-mail: tathimalta@gmail.com

Associate Editor:

Emmanuel Dias Neto

Conflict of Interest

The authors declare that no conflict of interest could be perceived as prejudicial to the impartiality of the reported research.

Authors Contributions

LO data curation, investigation, methodology, ELMER analysis, visualization, writing-original draft, writing-review and editing, data generation; LMMF investigation, data processing and analysis, writing-review and editing; IDE investigation, methodology, ELMER analysis; TMM project administration, conceptualization, formal analysis, supervision, visualization, writing-review and editing. All authors read and approved the final version.

TF	Biological Function	Oncogene or tumor suppressive		Ref
TF	Biological Function	Cancer	HNSCC	Ref
HMGA2	High cell proliferation, low apoptosis, tumor growth, promote angiogenesis, invasion, drug resistance and metastasis	Oncogene	Oncogene	(*Mansoori et al., 2021*Mansoori B, Mohammadi A, Ditzel HJ, Duijf PHG, Khaze V, Gjerstorff MF and Baradaran B (2021) HMGA2 as a critical regulator in cancer development. Genes (Basel) 12:269.)
HOXC6	Associated with chemotherapeutic resistance, lymph node metastasis, induce apoptosis and cell growth	Oncogene	Oncogene	(*Moon et al., 2012Moon S-M, Kim S-A, Yoon J-H and Ahn S-G (2012) HOXC6 is deregulated in human head and neck squamous cell carcinoma and modulates Bcl-2 expression. J Biol Chem 287:35678-35688.; Zhang et al., 2018*Zhang F, Ren C-C, Liu L, Chen Y-N, Yang L and Zhang X-A (2018) HOXC6 gene silencing inhibits epithelial-mesenchymal transition and cell viability through the TGF-β/smad signaling pathway in cervical carcinoma cells. Cancer Cell Int 18:204.)
POU5F1	tumor size, TNM stage, tumor differentiation, tumor invasion depth, lymph node metastasis, distant metastasis, lymphovascular invasion, vascular invasion, tumor number, and tumor recurrence	Oncogene	Oncogene	(*He et al., 2020*He D, Zhang X and Tu J (2020) Diagnostic significance and carcinogenic mechanism of pan-cancer gene POU5F1 in liver hepatocellular carcinoma. Cancer Med 9:8782-8800.)
SNAI2	lymph node metastasis, reduced overall survival, stem and/or progenitor cell biology, cellular differentiation, vascular remodeling and DNA damage repair	Oncogene	Oncogene	(*Wang et al., 2012Wang C, Liu X, Huang H, Ma H, Cai W, Hou J, Huang L, Dai Y, Yu T and Zhou X (2012) Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma. Int J Cancer 130:2249-2258.; Steinbichler et al., 2020*Steinbichler TB, Dudas J, Ingruber J, Glueckert R, Sprung S, Fleischer F, Cidlinsky N, Dejaco D, Kofler B, Giotakis AI et al. (2020) Slug is A surrogate marker of epithelial to mesenchymal transition (EMT) in head and neck cancer. J Clin Med 9:2061.)
SOX12	Tumor invasion, tumor differentiation, lymph node metastasis, distant metastasis	Oncogene	Oncogene	(*Seok et al., 2021Seok J, Gil M, Dayem AA, Saha SK and Cho S-G (2021) Multi-omics analysis of SOX4, SOX11, and SOX12 expression and the associated pathways in human cancers. J Pers Med 11:823.; Su et al., 2022*Su Z, Bao W, Yang G, Liu J and Zhao B (2022) SOX12 promotes thyroid cancer cell proliferation and invasion by regulating the expression of POU2F1 and POU3F1. Yonsei Med J 63:591-600.)

TF	Biological Function	Oncogene or tumor suppressive		Ref
TF	Biological Function	Cancer	HNSCC	Ref
HLF	Poorer progression-free survivals, cell growth, promotes anaerobic metabolism, distance metastasis and early relapse and progression	oncogene / tumor suppressive	tumor suppressive	(*Chen et al., 2020Chen J, Liu A, Lin Z, Wang B, Chai X, Chen S, Lu W, Zheng M, Cao T, Zhong M et al. (2020) Downregulation of the circadian rhythm regulator HLF promotes multiple-organ distant metastases in non-small cell lung cancer through PPAR/NF-κb signaling. Cancer Lett 482:56-71.; Liu B et al., 2021Liu B, Su Q, Ma J, Chen C, Wang L, Che F and Heng X (2021) Prognostic value of eight-gene signature in head and neck squamous carcinoma. Front Oncol 11:657002.; Li et al.*, 2022)
PAX1	Poor prognosis, apoptosis resistance, tumor cell proliferation and migration, repression of terminal differentiation, and finally progression of oral carcinogenesis	tumor suppressive	tumor suppressive	(*Huang et al., 2010Huang T-H, Lai H-C, Liu H-W, Lin CJ, Wang K-H, Ding D-C and Chu T-Y (2010) Quantitative analysis of methylation status of the PAX1 gene for detection of cervical cancer. Int J Gynecol Cancer 20:513-519.; Huang et al., 2014*Huang Y-K, Peng B-Y, Wu C-Y, Su C-T, Wang H-C and Lai H-C (2014) DNA methylation of PAX1 as a biomarker for oral squamous cell carcinoma. Clin Oral Investig 18:801-808.)
RARB	involved in suppressing cell growth and tumorigenicity, regulating gene expression and its retinoid-mediated antiproliferative, differentiative, immuno-modulatory, and apoptotic-inducing properties	tumor suppressive	tumor suppressive	(*Giannini et al., 1997Giannini F, Maestro R, Vukosavljevic T, Pomponi F and Boiocchi M (1997) All-trans, 13-cis and 9-cis retinoic acids induce a fully reversible growth inhibition in HNSCC cell lines: Implications for in vivo retinoic acid use. Int J Cancer 70:194-200.; Bebek et al., 2012*Bebek G, Bennett KL, Funchain P, Campbell R, Seth R, Scharpf J, Burkey B and Eng C (2012) Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma. Hum Mol Genet 21:1557-1565.)
ZNF471	poorer survival, suppressed cell proliferation, migration, and invasion	tumor suppressive	tumor suppressive	(*Bhat et al., 2016Bhat S, Kabekkodu SP, Noronha A and Satyamoorthy K (2016) Biological implications and therapeutic significance of DNA methylation regulated genes in cervical cancer. Biochimie 121:298-311.; Wang et al., 2020*Wang Q, Wu J, Huang H, Jiang Y, Huang Y, Fang H, Zheng G, Zhou X, Wu Y, Lei C et al. (2020) lncRNA LIFR-AS1 suppresses invasion and metastasis of non-small cell lung cancer via the miR-942-5p/ZNF471 axis. Cancer Cell Int 20:180.)
ZNF582	DNA damage response, proliferation, cell cycle control, and neoplastic transformation	tumor suppressive	tumor suppressive	(*Liu B et al., 2019Liu X, Zhao X and Gou C (2019) Identification of novel methylated DNA marker ZNF569 for head and neck squamous cell carcinoma. J Cancer 10:2250-2260.; Camuzi et al., 2021*Camuzi D, Simão TA, Dias F, Pinto LFR and Soares-Lima SC (2021) Head and neck cancers are not alike when tarred with the same brush: An epigenetic perspective from the cancerization field to prognosis. Cancers 13:5630. )

[1] *
These authors contributed equally to this study

Brasil

Brasil

Epigenomic integrative analysis pinpoint master regulator transcription factors associated with tumorigenesis in squamous cell carcinoma of oral tongue

Abstract