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Updated: Dec 19, 2025

Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells
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Profiling of Estrogen-regulated MicroRNAs in Breast Cancer Cells

Published on: February 21, 2014

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USP22 positively modulates ERα action via its deubiquitinase activity in breast cancer

Shengli Wang1, Xinping Zhong2, Chunyu Wang1

  • 1Department of Cell Biology, Key laboratory of Cell Biology, Ministry of Public Health, and Key laboratory of Medical Cell Biology, Ministry of Education, School of Life Sciences, China Medical University, Shenyang, 110122, Liaoning, China.

Cell Death and Differentiation
|June 5, 2020
PubMed

Insights

Histone deubiquitinase USP22 promotes breast cancer growth and endocrine resistance by maintaining estrogen receptor alpha (ERα) stability. High USP22 expression correlates with poorer survival in breast cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Estrogen receptor alpha (ERα) is central to ERα-positive breast cancer.
  • Endocrine therapies targeting ERα are common but face resistance.
  • ERα co-regulators can drive cancer development and endocrine resistance.

Purpose of the Study:

  • To identify novel co-regulators modulating ERα action.
  • To investigate the role of histone deubiquitinase USP22 in breast cancer.

Main Methods:

  • Comparative analysis of USP22 expression in breast cancer versus benign tissues.
  • Correlation analysis between USP22 expression and patient survival.
  • Assays to determine USP22's association with ERα and its effect on ERα stability and transactivation.
  • Investigation of USP22 recruitment to ERα target gene regulatory elements.
  • Functional studies of USP22 in breast cancer cells under various conditions.

Main Results:

  • USP22 is highly expressed in breast cancer tissues and linked to poorer overall survival.
  • USP22 associates with ERα, enhancing its stability and transactivation.
  • USP22 is recruited with ERα to target gene regulatory sites.
  • USP22 promotes breast cancer cell growth, even under hypoxia or anti-estrogen treatment.
  • USP22's deubiquitination activity is essential for its function.

Conclusions:

  • USP22 acts as a novel ERα co-regulator in breast cancer.
  • USP22 enhances ERα activity and promotes cell growth, contributing to endocrine resistance.
  • USP22 is a potential therapeutic target for overcoming endocrine resistance in breast cancer.

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