4.6 Article

A MYC-ZNF148-ID1/3 regulatory axis modulating cancer stem cell traits in aggressive breast cancer

期刊

ONCOGENESIS
卷 11, 期 1, 页码 -

出版社

SPRINGERNATURE
DOI: 10.1038/s41389-022-00435-1

关键词

-

类别

资金

  1. Royal Perth Hospital Medical Research Foundation
  2. Cancer Council of Western Australia(WA)
  3. Department of Health, Government of WA
  4. Walk for Women's Cancer Gift
  5. Department of Defense [BC200469]
  6. State Government
  7. Commonwealth Government

向作者/读者索取更多资源

In this study, researchers identified ZNF148 as a direct target of MYC in breast cancer. ZNF148 suppressed cell proliferation and migration and was transcriptionally repressed by MYC. Depletion of ZNF148 increased triple-negative breast cancer (TNBC) cell proliferation and migration. Mechanistically, ZNF148 was found to transcriptionally repress ID1 and ID3 expression, resulting in inhibition of cancer stem cell traits and plasticity. These findings uncover a previously unknown tumor suppressor role for ZNF148 and reveal a transcriptional regulatory circuitry involving MYC, ZNF148, and ID1/3 in driving aggressive breast cancer.
The MYC proto-oncogene (MYC) is one of the most frequently overexpressed genes in breast cancer that drives cancer stem cell-like traits, resulting in aggressive disease progression and poor prognosis. In this study, we identified zinc finger transcription factor 148 (ZNF148, also called Zfp148 and ZBP-89) as a direct target of MYC. ZNF148 suppressed cell proliferation and migration and was transcriptionally repressed by MYC in breast cancer. Depletion of ZNF148 by short hairpin RNA (shRNA) and CRISPR/Cas9 increased triple-negative breast cancer (TNBC) cell proliferation and migration. Global transcriptome and chromatin occupancy analyses of ZNF148 revealed a central role in inhibiting cancer cell de-differentiation and migration. Mechanistically, we identified the Inhibitor of DNA binding 1 and 3 (ID1, ID3), drivers of cancer stemness and plasticity, as previously uncharacterized targets of transcriptional repression by ZNF148. Silencing of ZNF148 increased the stemness and tumorigenicity in TNBC cells. These findings uncover a previously unknown tumor suppressor role for ZNF148, and a transcriptional regulatory circuitry encompassing MYC, ZNF148, and ID1/3 in driving cancer stem cell traits in aggressive breast cancer.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据