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Published on: August 23, 2019
SYT7 plays a role in promoting thyroid cancer by mediating HMGB3 ubiquitination
Shuai Dong1, Jun Pan1, Yi-Bin Shen1
1The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Abstract:
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.
Insights
SYT7 and HMGB3 are elevated in thyroid cancer, promoting tumor growth. SYT7 targets HMGB3 via BRCA1, inhibiting its ubiquitination and boosting cancer progression. Targeting SYT7 or HMGB3 may offer new thyroid cancer treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Thyroid cancer is a common endocrine malignancy requiring novel therapeutic targets.
- Understanding molecular mechanisms driving thyroid cancer progression is crucial for effective treatment strategies.
Purpose of the Study:
- To investigate the role of SYT7 and its downstream target HMGB3 in thyroid cancer.
- To elucidate the molecular mechanism by which SYT7 influences thyroid cancer progression.
Main Methods:
- Immunohistochemical staining, qPCR, and Western blot to assess SYT7 and HMGB3 expression.
- Cell function assays (proliferation, migration, apoptosis) to evaluate SYT7 and HMGB3 effects.
- In vivo tumor growth studies and molecular analyses (GeneChip, IPA, UbiBrowser, Co-IP) to determine the SYT7-BRCA1-HMGB3 pathway.
Main Results:
- SYT7 and HMGB3 expression were significantly upregulated in thyroid cancer tissues and cells.
- SYT7 knockdown inhibited thyroid cancer cell proliferation and migration while promoting apoptosis; overexpression had opposite effects.
- SYT7 interacted with BRCA1 to inhibit HMGB3 ubiquitination, leading to increased HMGB3 protein levels and promoting thyroid cancer progression.
Conclusions:
- SYT7 and HMGB3 are key drivers of thyroid cancer progression.
- The SYT7/BRCA1/HMGB3 axis represents a potential therapeutic target for thyroid cancer treatment.
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