Abnormal X chromosome inactivation and tumor development

被引:37
作者
Wang, Dan [1 ,2 ,3 ]
Tang, Le [2 ]
Wu, Yingfen [2 ]
Fan, Chunmei [2 ]
Zhang, Shanshan [1 ]
Xiang, Bo [2 ]
Zhou, Ming [2 ]
Li, Xiaoling [2 ]
Li, Yong [4 ]
Li, Guiyuan [2 ]
Xiong, Wei [2 ]
Zeng, Zhaoyang [2 ]
Guo, Can [1 ,2 ,3 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Stomatol, NHC Key Lab Carcinogenesis, Changsha, Hunan, Peoples R China
[2] Cent South Univ, Canc Res Inst, Chinese Minist Educ, Key Lab Carcinogenesis & Canc Invas, Changsha, Hunan, Peoples R China
[3] Cent South Univ, Xiangya Hosp 3, Dis Genome Res Ctr, Hunan Key Lab Nonresolving Inflammat & Canc, Changsha, Hunan, Peoples R China
[4] Baylor Coll Med, Dept Med, Dan L Duncan Comprehens Canc Ctr, Houston, TX 77030 USA
基金
中国国家自然科学基金;
关键词
X chromosome inactivation (XCI); Malignancy; Xist; Escape from X-inactivation tumor-suppressor; Sex differences; LONG NONCODING RNAS; XIST RNA; NUCLEAR LAMINA; DOSAGE COMPENSATION; SUPPRESSOR GENE; SEX DISPARITIES; HIGH EXPRESSION; BREAST-CANCER; STEM-CELLS; MUTATIONS;
D O I
10.1007/s00018-020-03469-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
During embryonic development, one of the two X chromosomes of a mammalian female cell is randomly inactivated by the X chromosome inactivation mechanism, which is mainly dependent on the regulation of the non-coding RNA X-inactive specific transcript at the X chromosome inactivation center. There are three proteins that are essential for X-inactive specific transcript to function properly: scaffold attachment factor-A, lamin B receptor, and SMRT- and HDAC-associated repressor protein. In addition, the absence of X-inactive specific transcript expression promotes tumor development. During the process of chromosome inactivation, some tumor suppressor genes escape inactivation of the X chromosome and thereby continue to play a role in tumor suppression. A well-functioning tumor suppressor gene on the idle X chromosome in women is one of the reasons they have a lower propensity to develop cancer than men, women thereby benefit from this enhanced tumor suppression. This review will explore the mechanism of X chromosome inactivation, discuss the relationship between X chromosome inactivation and tumorigenesis, and consider the consequent sex differences in cancer.
引用
收藏
页码:2949 / 2958
页数:10
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