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HJURP 通过 YAP1/NDRG1 转录轴调控三阴性乳腺癌细胞增殖和化疗耐药性。

HJURP regulates cell proliferation and chemo-resistance via YAP1/NDRG1 transcriptional axis in triple-negative breast cancer.

机构信息

Department of Surgical Oncology, Affiliated Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310000, Zhejiang, China.

Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, 310000, Zhejiang, China.

出版信息

Cell Death Dis. 2022 Apr 22;13(4):396. doi: 10.1038/s41419-022-04833-6.

DOI:10.1038/s41419-022-04833-6
PMID:35459269
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9033877/
Abstract

Triple-negative breast cancer is still a difficult point in clinical treatment at present, and a deep study of its pathogenesis has great clinical value. Therefore, our research mainly focuses on exploring the progression of triple-negative breast cancer and determines the important role of the HJURP/YAP1/NDRG1 transcriptional regulation axis in triple-negative breast cancer. We observed significantly increased HJURP expression levels in triple-negative breast cancer compared to other subtypes. HJURP could affect the level of ubiquitination modification of YAP1 protein and then regulate its downstream transcriptional activity. Mechanistically, we found that YAP1 positively regulates NDRG1 transcription by binding the promoter region of the NDRG1 gene. And HJURP/YAP1/NDRG1 axis could affect cell proliferation and chemotherapy sensitivity in triple-negative breast cancer. Taken together, these findings provide insights into the transcriptional regulation axis of HJURP/YAP1/NDRG1 in triple-negative breast cancer progression and therapeutic response.

摘要

三阴性乳腺癌仍然是目前临床治疗的难点，深入研究其发病机制具有重要的临床价值。因此，我们的研究主要集中在探讨三阴性乳腺癌的进展，并确定 HJURP/YAP1/NDRG1 转录调控轴在三阴性乳腺癌中的重要作用。我们观察到三阴性乳腺癌中 HJURP 的表达水平明显高于其他亚型。HJURP 可以影响 YAP1 蛋白的泛素化修饰水平，从而调节其下游的转录活性。从机制上讲，我们发现 YAP1 通过结合 NDRG1 基因启动子区域，正向调节 NDRG1 的转录。HJURP/YAP1/NDRG1 轴可影响三阴性乳腺癌细胞的增殖和化疗敏感性。综上所述，这些发现为 HJURP/YAP1/NDRG1 在三阴性乳腺癌进展和治疗反应中的转录调控轴提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78e/9033877/b49ef1bc5229/41419_2022_4833_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78e/9033877/b49ef1bc5229/41419_2022_4833_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e78e/9033877/ca6eb1c25c1b/41419_2022_4833_Fig1_HTML.jpg
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