miR-23b as a potential tumor suppressor and its regulation by DNA methylation in cervical cancer

Infectious Agents and Cancer

Gloria Fernández-Tilapa⁶  Berenice Illades-Aguiar²  Marco Antonio Jiménez-López¹  Luz Del Carmen Alarcón-Romero⁴  Daniel Hernández-Sotelo³  Diana Guillermina Soto-Flores⁶  Gricenda Torres-Altamirano⁶  Oscar Peralta-Zaragoza⁵  Hilda Jiménez-Wences⁶  Gabriela Elizabeth Campos-Viguri⁶ 

[1] Instituto Estatal de Cancerología “Dr. Arturo Beltrán Ortega”, Av. Adolfo Ruiz Cortines No. 128-A, Colonia Alta Progreso, Acapulco de Juárez C.P. 39570, Guerrero, México;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 C.P. 39089, Guerrero, México;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, Chilpancingo, C.P. 39089, Guerrero, México;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, Chilpancingo, C.P. 39089, Guerrero, México;Instituto Nacional de Salud Pública, Avenida Universidad No. 655, Colonia, Santa María Ahuacatitlán, Cuernavaca C.P. 62100, Morelos, México;Laboratorio de Investigación Clínica, Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Av. Lázaro Cárdenas S/N, Ciudad Universitaria, Colonia La Haciendita, Chilpancingo, C.P. 39089, Guerrero, México

关键词: zeb1;    c-met;    upa;    HPV16;    cervical cancer;    DNA methylation;    miR-23b;    expression;   

Others  :  1234564
DOI  :  10.1186/s13027-015-0037-6

 received in 2015-01-18, accepted in 2015-09-30,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Campos-Viguri et al.

【 图 表 】

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