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

Campos-Viguri GE, Jiménez-Wences H, Peralta-Zaragoza O, Torres-Altamirano G, Soto-Flores DG, Hernández-Sotelo D, Alarcón-Romero Ldel C, Jiménez-López MA, Illades-Aguiar B, Fernández-Tilapa G - Infect. Agents Cancer (2015)

Bottom Line: A value of p < 0.05 was considered statistically significant.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Expression of miR-23b in cervical scrapes from non-SILs and in tissues from patients diagnosed with LSIL, HSIL and cervical cancer. The expression of miR-23b was significantly lower in cervical cancer biopsies compared with LSIL and HSIL tissues. miR-92a was used for normalization of the data. *Statistically significant difference (p < 0.05)
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Fig4: Expression of miR-23b in cervical scrapes from non-SILs and in tissues from patients diagnosed with LSIL, HSIL and cervical cancer. The expression of miR-23b was significantly lower in cervical cancer biopsies compared with LSIL and HSIL tissues. miR-92a was used for normalization of the data. *Statistically significant difference (p < 0.05)

Mentions: The expression of miR-23b was significantly lower in non-SIL samples (p < 0.05) and in cervical cancer tissues (p < 0.05) than in tissues from patients diagnosed with LSIL and HSIL, (Fig. 4).Fig. 4


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

Campos-Viguri GE, Jiménez-Wences H, Peralta-Zaragoza O, Torres-Altamirano G, Soto-Flores DG, Hernández-Sotelo D, Alarcón-Romero Ldel C, Jiménez-López MA, Illades-Aguiar B, Fernández-Tilapa G - Infect. Agents Cancer (2015)

Expression of miR-23b in cervical scrapes from non-SILs and in tissues from patients diagnosed with LSIL, HSIL and cervical cancer. The expression of miR-23b was significantly lower in cervical cancer biopsies compared with LSIL and HSIL tissues. miR-92a was used for normalization of the data. *Statistically significant difference (p < 0.05)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4663735&req=5

Fig4: Expression of miR-23b in cervical scrapes from non-SILs and in tissues from patients diagnosed with LSIL, HSIL and cervical cancer. The expression of miR-23b was significantly lower in cervical cancer biopsies compared with LSIL and HSIL tissues. miR-92a was used for normalization of the data. *Statistically significant difference (p < 0.05)
Mentions: The expression of miR-23b was significantly lower in non-SIL samples (p < 0.05) and in cervical cancer tissues (p < 0.05) than in tissues from patients diagnosed with LSIL and HSIL, (Fig. 4).Fig. 4

Bottom Line: A value of p < 0.05 was considered statistically significant.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus