title: HERG1A potassium channel is the predominant isoform in head and neck squamous cell carcinomas: evidence for regulation by epigenetic mechanisms.
abstract: Evidences indicate that HERG1 voltage-gated potassium channel is frequently aberrantly expressed in various cancers including head and neck squamous cell carcinomas (HNSCC), representing a clinically and biologically relevant feature during disease progression and a potential therapeutic target. The present study further and significantly extends these data investigating for the first time the expression and individual contribution of HERG1 isoforms, their clinical significance during disease progression and also the underlying regulatory mechanisms. Analysis of HERG1A and HERG1B expression using real-time RT-PCR consistently showed that HERG1A is the predominant isoform in ten HNSCC-derived cell lines tested. HERG2 and HERG3 were also detected. Immunohistochemical analysis of HERG1A expression on 133 HNSCC specimens demonstrated that HERG1A expression increased during tumour progression and correlated significantly with reduced disease-specific survival. Furthermore, our study provides original evidence supporting the involvement of histone acetylation (i.e. H3Ac and H4K16Ac activating marks) in the regulation of HERG1 expression in HNSCC. Interestingly, this mechanism was also found to regulate the expression of another oncogenic channel (Kv3.4) as well as HERG2 and HERG3. These data demonstrate that HERG1A is the predominant and disease-relevant isoform in HNSCC progression, while histone acetylation emerges as an important regulatory mechanism underlying Kv gene expression.
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: Sofía T
authors.initials: ST
authors.lastname: Menéndez
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: M Ángeles
authors.initials: MÁ
authors.lastname: Villaronga
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: Juan P
authors.initials: JP
authors.lastname: Rodrigo
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: Saúl
authors.initials: S
authors.lastname: Álvarez-Teijeiro
authors.affiliation: Unidad de Epigenética del Cáncer, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Spain.
authors.forename: Rocío G
authors.initials: RG
authors.lastname: Urdinguio
authors.affiliation: Unidad de Epigenética del Cáncer, Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, Spain.|Department of Immunology and Oncology, National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid E-28049, Spain.
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Suárez
authors.affiliation: Servicio de Otorrinolaringología, Hospital Universitario Central de Asturias and Instituto Universitario de Oncología del Principado de Asturias, Oviedo, Spain.
authors.forename: Juana M
authors.initials: JM
authors.lastname: García-Pedrero
mesh_terms: D000107:Acetylation; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D044127:Epigenesis, Genetic; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics* / Q000378:metabolism; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D020033:Protein Isoforms; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; D006657:Histones; C496884:KCNH1 protein, human; D020033:Protein Isoforms