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调控人绒毛膜促性腺激素β亚基在卵巢癌中的表达。

Regulation of human chorionic gonadotropin beta subunit expression in ovarian cancer.

机构信息

Department of Cell Biology, Poznan University of Medical Sciences, 5D Rokietnicka Street, 60-806, Poznan, Poland.

Gynaecologic Oncology Department, Poznan University of Medical Sciences, 33 Polna Street, 60-101, Poznan, Poland.

出版信息

BMC Cancer. 2019 Jul 30;19(1):746. doi: 10.1186/s12885-019-5960-2.

DOI:10.1186/s12885-019-5960-2
PMID:31362717
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6664497/
Abstract

PURPOSE

Expression of human chorionic gonadotropin beta subunit by cancers is extensively documented, yet regulation of the multiple genes that can code for this protein is poorly understood. The aim of the study was to examine the mechanisms regulating CGB gene expression in ovarian cancer.

METHODS

Expression of CGB genes and SP1, SP3, TFAP2A transcription factor genes was evaluated by RT-qPCR. The methylation status of CGB genes promoter regions was examined by methylation-specific PCR.

RESULTS

mRNA arising from multiple CGB genes was detected in both ovarian control and malignant tissues. However, expression of CGB3-9 genes was shown to be significantly higher in malignant than healthy ovarian tissues. CGB1 and CGB2 transcripts were shown to be present in 20% of ovarian cancers, but were not detected in any of the control samples. Malignant tissues were characterized by DNA demethylation of CGB promoter regions. In ovarian cancer CGB expression positively correlated with TFAP2A transcripts level and expression of TFAP2A transcription factor was significantly higher in cancer than in control tissues. In contrast SP3 expression level was significantly lower in ovarian tumours than in control ovarian tissue.

CONCLUSIONS

In ovarian cancers increased expression of human chorionic gonadotropin beta subunit is associated with demethylation of CGB promoter regions. CGB3-9 expression level strongly correlates with expression of the TFAP2A transcription factor. Presence of mRNA arising from CGB1 and CGB2 genes appears to be a unique feature of a subset of ovarian cancers.

摘要

目的

人类绒毛膜促性腺激素β亚基在癌症中的表达已被广泛证实,但对能编码该蛋白的多个基因的调控知之甚少。本研究旨在探讨卵巢癌中 CGB 基因表达的调控机制。

方法

通过 RT-qPCR 评估 CGB 基因和 SP1、SP3、TFAP2A 转录因子基因的表达。通过甲基化特异性 PCR 检测 CGB 基因启动子区域的甲基化状态。

结果

在卵巢对照和恶性组织中均检测到来自多个 CGB 基因的 mRNA。然而,CGB3-9 基因的表达在恶性组织中明显高于健康卵巢组织。CGB1 和 CGB2 转录本在 20%的卵巢癌中存在,但在任何对照样本中均未检测到。恶性组织表现为 CGB 启动子区域的 DNA 去甲基化。在卵巢癌中,CGB 表达与 TFAP2A 转录本水平呈正相关,且 TFAP2A 转录因子的表达在癌症组织中明显高于对照组织。相比之下,SP3 在卵巢肿瘤中的表达明显低于对照卵巢组织。

结论

在卵巢癌中,人绒毛膜促性腺激素β亚基的高表达与 CGB 启动子区域的去甲基化有关。CGB3-9 的表达水平与 TFAP2A 转录因子的表达强烈相关。CGB1 和 CGB2 基因的 mRNA 存在似乎是卵巢癌亚群的一个独特特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0e4/6664497/962730d60fc9/12885_2019_5960_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0e4/6664497/53b0ab389bd0/12885_2019_5960_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0e4/6664497/7a61d45eba14/12885_2019_5960_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0e4/6664497/962730d60fc9/12885_2019_5960_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0e4/6664497/53b0ab389bd0/12885_2019_5960_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0e4/6664497/7a61d45eba14/12885_2019_5960_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e0e4/6664497/962730d60fc9/12885_2019_5960_Fig3_HTML.jpg

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