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SYT7 plays a role in promoting thyroid cancer by mediating HMGB3 ubiquitination

in Endocrine-Related Cancer
Authors:
Shuai Dong The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Jun Pan The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Yi-Bin Shen The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Li-Xian Zhu The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Liang Chen The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Feng Zhu The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Hui Li Zhejiang University, Hangzhou, Zhejiang, China

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Hai-Xiang Shen Zhejiang University, Hangzhou, Zhejiang, China

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Qing Xia People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China

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Yi-Jun Wu The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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Xiao-Jun Xie The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China

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https://orcid.org/0000-0002-4173-1067

Correspondence should be addressed to Q Xia or Y-J Wu or X-J Xie: xiaqing_zj@163.com or wuwu5925@zju.edu.cn or xxj701023@zju.edu.cn

*(S Dong and J Pan contributed equally to this work)

DOI:
https://doi.org/10.1530/ERC-21-0146
Volume/Issue:
Volume 29: Issue 4
Article Type:
Research Article
Page Range:
175–189
Online Publication Date:
01 Mar 2022
Copyright:
© Society for Endocrinology 2022
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Thyroid cancer is one of the most common endocrine malignancies. It is necessary to discover more effective molecular targets for the treatment of thyroid cancer. The results of immunohistochemical staining, qPCR and Western blot indicated that the expression of SYT7 in thyroid cancer tissues and cells was higher than that in paracarcinoma tissues and normal thyroid cells. Through cell function testing experiments, it was found that SYT7 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis, while SYT7 overexpression had the opposite effect. Similarly, SYT7 downregulation also suppressed tumor growth in vivo. HMGB3 was confirmed to be the downstream gene of SYT7 by GeneChip and Ingenuity Pathway Analysis. Besides, through UbiBrowser database predictions and Co-IP assays, we found that SYT7 interacted with BRCA1 to inhibit HMGB3 ubiquitination and thus upregulated the protein level of HMGB3. Similar to SYT7, HMGB3 was significantly upregulated in thyroid cancer. HMGB3 knockdown inhibited the proliferation and migration of thyroid cancer cells and promoted cell apoptosis. Furthermore, HMGB3 knockdown restored the promotion of cell proliferation and migration caused by SYT7 overexpression. SYT7 and HMGB3 were upregulated in thyroid cancer, and SYT7 regulated the expression of HMGB3 through BRCA1-mediated ubiquitination of HMGB3 to promote thyroid cancer progression.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
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Copyright:
© Society for Endocrinology 2022
Page(s):
15
Received Date:
22 Nov 2021
Accepted Date:
24 Jan 2022
Print Publication Date:
01 Apr 2022
Online Publication Date:
01 Mar 2022
Keywords:
thyroid cancer; SYT7; HMGB3; proliferation; migration; apoptosis

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