title: miR-23b as a potential tumor suppressor and its regulation by DNA methylation in cervical cancer.
abstract: BACKGROUND
  The aberrant expression of miR-23b is involved in the development and progression of cancer. The aim of this study was to evaluate the potential role of methylation in the silencing of miR-23b in cervical cancer cell lines and to determine its expression in stages of malignant progression and in cervical cancer tissues HPV16-positive.
  
  
  METHODS
  The methylation of the miR-23b promoter was determined in HeLa, SiHa, CaSki and C33A cells using a Human Cancer miRNA EpiTectMethyl II Signature PCR Array®. The cells were treated with 5-Aza-2'-deoxycytidine, and the expression of miR-23b, uPa, c-Met and Zeb1 was determined by qRT-PCR. miR-92a and GAPDH were used as controls. The expression of miR-23b was determined in cervical scrapes and biopsies of women without squamous intraepithelial lesions, with precursor lesions and with cervical cancer, all were HPV16-positive. The Fisher exact and Mann-Whitney tests were used to compare the differences of the expression of miR-23b, uPa, c-Met and Zeb1 among cell groups, and the difference among patients, respectively. The association between the expression of miR-23b and cervical cancer was determined by logistic regression with a confidence level of 95 %. A value of p < 0.05 was considered statistically significant.
  
  
  RESULTS
  In C33A, HeLa and CaSki cells, methylation was associated with decreased expression of miR-23b. After treatment with 5-Aza-CdR, the expression of miR-23b increased in all cell lines and the expression of c-Met decreased in HeLa cells, while uPa and Zeb1 decreased in C33A and CaSki cells. In SiHa cells the expression of uPa, c-Met and Zeb1 increased. The expression of miR-23b decreased in relation to the increase in the severity of the lesion and was significantly lower in cervical cancer. In women with premalignant lesions HPV16-positive, decreased levels of miR-23b increased the risk of cervical cancer (OR = 36, 95 % CI = 6.7-192.6, p < 0.05).
  
  
  CONCLUSIONS
  The results suggest that the expression of miR-23b is regulated by the methylation of its promoter and is possible that this microRNA influence the expression of uPa, c-Met and Zeb1 in cervical cancer cells lines. In women with premalignant lesions and cervical cancer infected with HPV16, the expression level of miR-23b agree with a tumor suppressor gene.
authors.affiliation: Laboratorio de Investigación Clínica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, C.P. 39089 Chilpancingo, Guerrero México.
authors.forename: Gabriela Elizabeth
authors.initials: GE
authors.lastname: Campos-Viguri
authors.affiliation: Laboratorio de Investigación Clínica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, C.P. 39089 Chilpancingo, Guerrero México.
authors.forename: Hilda
authors.initials: H
authors.lastname: Jiménez-Wences
authors.affiliation: Instituto Nacional de Salud Pública, Avenida Universidad No. 655, Colonia, Santa María Ahuacatitlán, Cuernavaca, Morelos C.P. 62100 México.
authors.forename: Oscar
authors.initials: O
authors.lastname: Peralta-Zaragoza
authors.affiliation: Laboratorio de Investigación Clínica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, C.P. 39089 Chilpancingo, Guerrero México.
authors.forename: Gricenda
authors.initials: G
authors.lastname: Torres-Altamirano
authors.affiliation: Laboratorio de Investigación Clínica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, C.P. 39089 Chilpancingo, Guerrero México.
authors.forename: Diana Guillermina
authors.initials: DG
authors.lastname: Soto-Flores
authors.affiliation: Laboratorio de Virología y Epigenética del Cáncer, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, C.P. 39089 Chilpancingo, Guerrero México.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hernández-Sotelo
authors.affiliation: Laboratorio de Investigación en Citopatología e Histoquímica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, C.P. 39089 Chilpancingo, Guerrero México.
authors.forename: Luz Del Carmen
authors.initials: Ldel C
authors.lastname: Alarcón-Romero
authors.affiliation: Instituto Estatal de Cancerología "Dr. Arturo Beltrán Ortega", Av. Adolfo Ruiz Cortines No. 128-A, Colonia Alta Progreso, Acapulco de Juárez, Guerrero C.P. 39570 México.
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Jiménez-López
authors.affiliation: Laboratorio de Biomedicina Molecular, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo, Guerrero C.P. 39089 México.
authors.forename: Berenice
authors.initials: B
authors.lastname: Illades-Aguiar
authors.affiliation: Laboratorio de Investigación Clínica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, C.P. 39089 Chilpancingo, Guerrero México.
authors.forename: Gloria
authors.initials: G
authors.lastname: Fernández-Tilapa
keywords: DNA methylation; HPV16; c-met; cervical cancer; expression; miR-23b; upa; zeb1