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Abnormal X chromosome inactivation and tumor development

Abstract

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.

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Acknowledgements

This study was supported by grants from The National Natural Science Foundation of China (81672683, 81672993, 81702907, 81772928, 81803025, 81872278, and 81972776), the Natural Science Foundation of Hunan Province (2018SK21210, 2018SK21211, 2018JJ3704, 2018JJ3815, and 2017SK2105) and the Fundamental Research Funds for the Central Universities of Central South University (2019zzts712 and 2019zzts089).

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Correspondence to Can Guo.

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Wang, D., Tang, L., Wu, Y. et al. Abnormal X chromosome inactivation and tumor development. Cell. Mol. Life Sci. (2020). https://doi.org/10.1007/s00018-020-03469-z

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Keywords

  • X chromosome inactivation (XCI)
  • Malignancy
  • Xist
  • Escape from X-inactivation tumor-suppressor
  • Sex differences