雄激素受体基因CAG短串联重复序列与肿瘤发生和预后的关联研究进展

谢佳新; 沈舒宁

doi:10.16462/j.cnki.zhjbkz.2020.03.021

雄激素受体基因CAG短串联重复序列与肿瘤发生和预后的关联研究进展

doi: 10.16462/j.cnki.zhjbkz.2020.03.021

谢佳新^1, ,,
沈舒宁²

1.
400038 重庆, 陆军军医大学高原军事医学系高原作业医学教研室, 极端环境医学教育部重点实验室, 全军高原医学重点实验室
2.
100094 北京, 解放军第984医院

基金项目: 国家自然科学基金(81803294);河北省自然科学基金(H2015509001)

详细信息

通讯作者:
谢佳新, E-mail:xiejiaxin1006@163.com

中图分类号: R373.21;R512.6;R181
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- 被引次数: 0
出版历程
- 收稿日期: 2019-07-10
- 修回日期: 2019-09-17
- 刊出日期: 2020-03-10

Review on the association of CAG short tandem repeats of androgen receptor gene with tumorigenesis and prognosis

XIE Jia-xin^{1
, ,},
SHEN Shu-ning²

1.
Department of High Altitude Operation Medicine, College of High Altitude Military Medicine, Army Medical University, Key Laboratory of Extreme Environmental Medicine, Ministry of Education of China, Key Laboratory of High Altitude Medicine, PLA, Chongqing 400038, China
2.
The 984th Hospital of PLA, Beijing 100094, China

Funds: National Natural Science Foundation of China(81803294); Natural Science Foundation of Hebei Province(H2015509001)

More Information

Corresponding author: XIE Jia-xin, E-mail:xiejiaxin1006@163.com

摘要

摘要: 雄激素受体(androgen receptor, AR)及其介导的信号通路异常与人类多种疾病的发生、转归及预后密切相关, 并在一定程度上导致疾病的性别差异, 其具体机制尚不明确。AR基因第1外显子CAG短串联重复序列(short tandem repeat, STR)与AR转录调节活性存在负相关性, 影响靶蛋白合成与生物学功能, 在前列腺癌、乳腺癌、膀胱癌、肝癌、子宫内膜癌等多种肿瘤发生发展及预后中扮演重要角色。本文对目前AR基因CAG STR与常见肿瘤相关性研究进行综述, 为进一步探索AR导致相关肿瘤高发和性别差异作用机制和筛选肿瘤高危人群提供线索。
- 雄激素受体 /
- 肿瘤 /
- 短串联重复序列 /
- 多态性
Abstract: Abnormal expression of androgen receptor(AR) and AR-mediated signaling pathways are closely related to the occurrence, outcome, and prognosis of various human disease, and to some extent, AR lead to gender differences in these diseases. However, the specific mechanism is still unclear. CAG short tandem repeat(STR) sequence in exon 1 of AR gene negatively correlates with the transcriptional regulation activity, affects the synthesis and biological function of the target proteins, and plays an important role in the development and prognosis of various tumors, such as prostate cancer, breast cancer, bladder cancer, liver cancer, and endometrial cancer. In this review, we summarized the current studies on the association between AR gene CAG STR and the common tumors, in order to provide clues for further exploring the mechanism of AR-related tumors with high incidence and gender differences, and screening populations with high risk for the corresponding tumors.
- Androgen receptor /
- Tumor /
- Short tandem repeat /
- Polymorphism

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图 1 雄激素受体信号通路示意图

Figure 1. The schematic map of androgen receptor signaling pathway

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表 1 AR基因CAG重复序列多态性在常见肿瘤发生发展中的作用

Table 1. The role of CAG repeat polymorphism of AR gene in the occurrence and development of common tumors

肿瘤	作用因子或信号通路	作用特点
前列腺癌	EGF、TGF-β、IGF1、Wnt/β-Catenin、miR-4496、miRNA-200a	汉族人群中短(CAG)n增加发病风险, 且恶性程度高, 国外人群中相关性尚不确定
乳腺癌	ER、PR、HER-2、E-cadherin、Cyclin D1、p21、p27	长(CAG)n增加发病风险, 提示不良预后
膀胱癌	CD24、UGT1A、Wnt/β-catenin、c-myc、p53、TGF-β、E-cadherin、EGFR、ERBB2	短(CAG)n增加发病风险;
肝癌	HBx、TGF-β1、VEGF、CCRK、miR-216a、p38、NF-ΚB/MMP9	短(CAG)n增加男性发病风险, 预后差; 长(CAG)n在HBV阳性, 尤其是具有肝癌家族史女性中常见
子宫内膜癌	IGF-1R、Cyclin D1、PI3K/MAPK、CD133	国外女性中长(CAG)n增加发病风险, 汉族女性未见报道

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