5-Aza-2’-deoxycytidine may influence the proliferation and apoptosis of cervical cancer cells via demethylation in a dose- and time-dependent manner

Yao, Tingting; Mo, Saijun; Liu, L Y; Lü, Hongyan; Huang, Mengzhu; Lin, Zhihong

doi:10.4238/2013.february.4.5

Cited by 11 publications

(7 citation statements)

References 17 publications

(17 reference statements)

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“…Yet, motility-associated genes in invasive and motile MDA-MB-231 cells might have already been active even before the AZA treatment, so only gene expression and protein kinase regulation pathways were enriched upon AZA treatment. Commonly induced pathways in both cell lines were those relatively known as characteristics of the AZA effect on cancer cell lines [ 44 – 47 ], while commonly downregulated pathways mostly consisted of the cell cycle, cell division and metabolism-related pathways, potentially resulting in cessation of cell growth and proliferation when deactivated, enabling AZA’s anti-cancer effect. Yet, most of these downregulated genes could be possibly repressed due to secondary effects of AZA treatment, as it caused induction of several transcription regulatory genes.…”

Section: Discussionmentioning

confidence: 99%

Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

et al. 2015

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BackgroundCpG hypermethylation in gene promoters is a frequent mechanism of tumor suppressor gene silencing in various types of cancers. It usually occurs at early steps of cancer progression and can be detected easily, giving rise to development of promising biomarkers for both detection and progression of cancer, including breast cancer. 5-aza-2′-deoxycytidine (AZA) is a DNA demethylating and anti-cancer agent resulting in induction of genes suppressed via DNA hypermethylation.ResultsUsing microarray expression profiling of AZA- or DMSO-treated breast cancer and non-tumorigenic breast (NTB) cells, we identified for the first time TAGLN gene as a target of DNA hypermethylation in breast cancer. TAGLN expression was significantly and frequently downregulated via promoter DNA hypermethylation in breast cancer cells compared to NTB cells, and also in 13/21 (61.9 %) of breast tumors compared to matched normal tissues. Analyses of public microarray methylation data showed that TAGLN was also hypermethylated in 63.02 % of tumors compared to normal tissues; relapse-free survival of patients was worse with higher TAGLN methylation; and methylation levels could discriminate between tumors and healthy tissues with 83.14 % sensitivity and 100 % specificity. Additionally, qRT-PCR and immunohistochemistry experiments showed that TAGLN expression was significantly downregulated in two more independent sets of breast tumors compared to normal tissues and was lower in tumors with poor prognosis. Colony formation was increased in TAGLN silenced NTB cells, while decreased in overexpressing BC cells.ConclusionsTAGLN gene is frequently downregulated by DNA hypermethylation, and TAGLN promoter methylation profiles could serve as a future diagnostic biomarker, with possible clinical impact regarding the prognosis in breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0138-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

et al. 2015

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“…[29] As we reported the apoptotic effect of 5-Aza-CdR, it has demonstrated that 5-Aza-CdR can induce apoptosis in human Caco-2 colonic carcinoma cell line,[30] human HCC cell line Huh7,[31] HCC cell line SMMC-7721 and HepG2,[32] and Hela cells. [33]…”

Section: Discussionmentioning

confidence: 99%

Effect of 5-aza-2'-deoxycytidine in comparison to valproic acid and trichostatin A on histone deacetylase 1, DNA methyltransferase 1, and CIP/KIP family (p21, p27, and p57) genes expression, cell growth inhibition, and apoptosis induction in colon cancer SW480 cell line

Sanaei

Kavoosi

2019

Adv Biomed Res

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Background: Cancer initiation and progression depends on genetic and epigenetic alterations such as DNA methylation and histone modifications. Hypermethylation and deacetylation of the CIP/KIP family (p21, p27, and p57) lead to tumorigenesis. Our previous study indicated that DNA methyltransferase (DNMT) inhibitor and histone deacetylase (HDAC) inhibitors can inhibit cell growth and induce apoptosis. The aim of the present study was to investigate the effect of 5-Aza-2'-deoxycytidine (5-Aza-CdR) in comparison to valproic acid (VPA) and trichostatin A (TSA) on HDAC1, DNMT1, and CIP/KIP family (p21, p27, and p57) genes expression, cell growth inhibition, and apoptosis induction in colon cancer SW480 cell line. Materials and Methods: The effect of the compounds on the cell viability was measured by MTT assay. The expression of HDAC1, DNMT1, and CIP/KIP family (p21, p27, and p57) genes was evaluated by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). For the detection of cell apoptosis, apoptotic cells were examined by the Annexin V-FITC/PI detection kit. Results: The results of MTT assay indicated that 5-Aza-CdR, VPA, and TSA significantly inhibited cell growth ( P < 0.002, P < 0.001, and P < 0.001, respectively). The results of real-time RT-PCR demonstrated that all compounds significantly down-regulated DNMT1 and HDAC1, and up-regulated p21, p27, and p57 genes expression. The result of flow cytometry assay revealed that all agents induced apoptosis significantly. Conclusion: 5-Aza-CdR, VPA, and TSA can significantly downregulate DNMT1 and HDAC1 and up-regulate p21, p27, and p57 genes expression through which enhance cell apoptosis and cell growth inhibition in colon cancer.

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“…We also proved that miR-21 is involved in cervical squamous cell tumorigenesis by CCL20 (Yao T, et al, [10]). 5-Aza-CdR which can reactivate the expression of methylated tumor suppressor genes, is a pyrimidine nucleoside analog that forms a covalent complex with DNMT during DNA replication (Yao TT, et al, [11]). To evaluate if an aberrant DNA methylation pattern could also contribute to the altered miRNA expression characterizing the cervical carcinoma, we analyzed the miRNA profiling of the cervical cancer cell lines before and after treatment with 5-AZA.…”

Section: Discussionmentioning

confidence: 99%

Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in cervical cancer

Yao

Rao

Liu

et al. 2013

Virol J

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BackgroundMultiple studies proved that miRNAs have a causal role in tumorigenesis. Some miRNAs are regulated by epigenetic alterations in their promoter regions and can be activated by chromatin- modifying drugs.MethodsWe treated cervical cancer cells with 5-aza-2’-deoxycytidine and get a microarray analysis. Dysregulation of miRNAs was measured by qPCR in cervical cell lines and methylation status of them in cervical cancer tissue were performed with MeDIP-qPCR assay.ResultsWe found hypermethylation of miR-432, miR-1286, miR-641, miR-1290, miR-1287 and miR-95 may have some relationship with HPV infection in cervical cell lines. In primary tumors of cervix with paired normal tissue, expression levels of miRNAs were inversely correlated with their DNA methylation status in the cervical cancer cell lines treated with 5-AZA.ConclusionsOur results indicate that miRNAs might play a role in the pathogenesis of human cervical cancer with HPV and identify altered miRNA methylation as a possible epigenetic mechanism involved in their aberrant expression.

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5-Aza-2’-deoxycytidine may influence the proliferation and apoptosis of cervical cancer cells via demethylation in a dose- and time-dependent manner

Cited by 11 publications

References 17 publications

Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

Effect of 5-aza-2'-deoxycytidine in comparison to valproic acid and trichostatin A on histone deacetylase 1, DNA methyltransferase 1, and CIP/KIP family (p21, p27, and p57) genes expression, cell growth inhibition, and apoptosis induction in colon cancer SW480 cell line

Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in cervical cancer

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