Cervical cancer-associated promoter polymorphism affects akna expression levels.
Cervical cancer (CC) is responsible for >260,000 deaths worldwide each year. Efforts are being focused on identifying genetic susceptibility factors, especially in genes related to the immune response. Akna has been proposed to be one of them, but data regarding its functional role in the disease is scarce. Supporting the notion of akna as a CC susceptibility gene, we found two polymorphisms associated with squamous intraepithelial lesion (SIL) and CC; moreover, we identified an association between high akna expression levels and CC and SIL, but its direction differs in each disease stage. To show the potential existence of a cis-acting polymorphism, we assessed akna allelic expression imbalance for the alleles of the -1372C>A polymorphism. We found that, regardless of the study group, the number of transcripts derived from the A allele was significantly higher than those from the C allele. Our results support the hypothesis that akna is a CC susceptibility genetic factor and suggest that akna transcriptional regulation has a role in the disease. We anticipate our study to be a starting point for in vitro evaluation of akna transcriptional regulation and for the identification of transcription factors and cis-elements regulating AKNA function that are involved in carcinogenesis.
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
G A
GA
Martínez-Nava
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
K
K
Torres-Poveda
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
A
A
Lagunas-Martínez
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
M
M
Bahena-Román
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
M A
MA
Zurita-Díaz
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
E
E
Ortíz-Flores
Unidad de Investigación Biomédica en Cáncer, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Cancerología, Secretaría de Salud, Distrito Federal, Mexico.
A
A
García-Carrancá
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
V
V
Madrid-Marina
193;rea de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Mexico.
A I
AI
Burguete-García
D000328:Adult; D000368:Aged; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics*; D055815:Young Adult
C423232:AKNA protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors