Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion.
Methylation-mediated silencing of EDN3 promotes cervical cancer proliferation, migration and invasion.
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甲基化介导的 EDN3 沉默促进宫颈癌增殖、迁移和侵袭。
DOI：
10.3389/fonc.2023.1010132
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
宫颈癌（CC）仍然是世界范围内癌症相关死亡的主要原因之一。然而，宫颈癌发生前可发生癌前宫颈上皮内瘤变（CIN），在变为恶性前可持续长达20年。因此，早期筛查是防止宫颈病变发展为浸润性宫颈癌，降低发病率的关键。这些基因在癌症中下调和高甲基化，可能为宫颈癌提供潜在的药物靶点。在我们目前的研究中，我们使用来自基因表达Omnibus （GEO）和癌症基因组图谱（TCGA）数据库的数据集，我们发现内皮素3 （EDN3）在宫颈鳞状细胞癌（CSCC）中下调和高甲基化。在GSE63514 （n=128）数据集和我们的样本（n=221）中进一步分析发现，EDN3的表达随着宫颈病变程度的降低而降低。我们对样本（n=469）中EDN3启动子区域的4个CpG位点进行了焦磷酸测序。数据表明，EDN3的甲基化水平随着宫颈病变程度的增加而升高。DNA甲基转移酶1 （DNMT1）抑制剂5-氮杂胞苷（5-Aza）可阻断甲基化介导的EDN3沉默。采用乙炔脱氧尿苷（EdU）法、自愈法、克隆形成法和transwell法研究EDN3在宫颈癌细胞系中的生物学功能。这些实验结果证实，过表达EDN3可以抑制宫颈癌细胞的增殖、克隆形成、迁移和侵袭。EDN3可能为CSCC提供潜在的生物标志物和治疗靶点。
Cervical cancer (CC) remains one of the leading causes of cancer-related deaths worldwide. However, cervical cancer is preceded by the pre-malignant cervical intraepithelial neoplasia (CIN) that can last for up to 20 years before becoming malignant. Therefore, early screening is the key to prevent the progression of cervical lesions into invasive cervical cancer and decrease the incidence. The genes, down-regulated and hypermethylated in cancers, may provide potential drug targets for cervical cancer. In our current study, using the datasets from Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases, we found that endothelin 3 (EDN3) was downregulated and hypermethylated in cervical squamous cell carcinoma (CSCC). The further analysis in GSE63514 (n=128) dataset and in our samples (n=221) found that the expression of EDN3 was decreased with the degree of cervical lesions. Pyrosequencing was performed to evaluate 4 CpG sites of the EDN3 promoter region in our samples (n=469). The data indicated that the methylation level of EDN3 was increased with the degree of cervical lesions. EDN3 silencing mediated by methylation can be blocked by 5-Azacytidine (5-Aza), a DNA methyltransferase 1 (DNMT1) inhibitor, treatment in cervical cancer cell lines. Ethynyldeoxyuridine (EdU) assay, would-healing assay, clone formation assay and transwell assay were conducted to investigate the biological function of EDN3 in cervical cancer cell lines. The results of these experiments confirmed that overexpression of EDN3 could inhibit the proliferation, clone formation, migration and invasion of cervical cancer cells. EDN3 may provide potential biomarker and therapeutic target for CSCC.
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影响因子：
3
作者：
Bardou P;Mariette J;Escudié F;Djemiel C;Klopp C
通讯作者：
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影响因子：
5.7
作者：
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Li, Lei
影响因子：
11.2
作者：
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Schuebel, KE
影响因子：
6.4
作者：
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通讯作者：
Wentzensen N
DOI：
10.1158/1541-7786.mcr-10-0563
发表时间：
2011-12
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Liu Y;Ye F;Yamada K;Tso JL;Zhang Y;Nguyen DH;Dong Q;Soto H;Choe J;Dembo A;Wheeler H;Eskin A;Schmid I;Yong WH;Mischel PS;Cloughesy TF;Kornblum HI;Nelson SF;Liau LM;Tso CL
通讯作者：
Tso CL