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Published on: May 11, 2016
UBC Mediated by SEPT6 Inhibited the Progression of Prostate Cancer
Ruochen Zhang1, Yaojing Yang1, Haijian Huang1
1Shengli Clinical Medical College of Fujian Medical University, Department of Urology, Fujian Provincial Hospital, China.
Background:
Prostate cancer is one of the most common malignancies in men. Protein ubiquitination is an important mechanism for regulating protein activity and level in vivo. We aimed to study the mechanism of SEPT6 and UBC action in prostate cancer to identify new targets.
Methods:
The ubiquitin-protein and the ubiquitin coding gene UBA52, UBA80, UBB, and UBC expressions were detected in clinical tissues and cells. Overexpression and knockdown of UBC were performed in prostate cancer DU145 cells. Cell Counting Kit 8 (CCK-8) assay was performed to detect cell proliferation. Cell cycle at 24 h was detected by flow cytometry. Clonal formation assay was used to measure cell clone number. Immunofluorescence (IF) was performed to detect the colocalization of SEPT6 and UBC in prostate cancer cells. Next, we overexpressed or knocked down SEPT6 expression in DU145 cells. Pearson correlation coefficient was applied to analyze the relationship between SEPT6 and UBC in prostate cancer tissue. oe-SEPT6+oe-UBC coexpressing cells were constructed to detect the upstream and downstream relationship between SEPT6 and UBC on prostate cancer cells. The tumor formation experiment was performed to explore SEPT6/UBC effect on prostate cancer.
Results:
UBC was upregulated in prostate cancer tissues and cells. Overexpression of UBC promoted cell survival and proliferation. IF revealed the colocalization of SEPT6 and UBC in prostate cancer cells. UBC expression decreased after oe-SEPT6, while increased after sh-SEPT6, indicating that UBC was downstream of SEPT6. Pearson correlation coefficient analysis showed that SEPT6 was negatively correlated with UBC in prostate cancer tissues. SEPT6 as an upstream gene of UBC regulated prostate cancer cell behavior through UBC. The tumor formation experiment showed that SEPT6 could inhibit tumor growth.
Conclusion:
In general, SEPT6 inhibited UBC expression, thereby reducing the overall ubiquitination level, affecting the expression level of downstream cell proliferation-related genes, and then affecting the progression of prostate cancer.
Insights
SEPT6 inhibits prostate cancer progression by downregulating UBC expression, reducing ubiquitination, and affecting cell proliferation. This study identifies SEPT6 and UBC as potential therapeutic targets for prostate cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate cancer is a prevalent malignancy in men.
- Protein ubiquitination is a key regulator of protein activity and levels.
- Understanding the roles of SEPT6 and UBC in prostate cancer is crucial for identifying new therapeutic targets.
Purpose of the Study:
- To investigate the mechanistic roles of SEPT6 and UBC in prostate cancer.
- To explore the relationship between SEPT6 and UBC in prostate cancer progression.
- To identify potential therapeutic targets for prostate cancer treatment.
Main Methods:
- Detected expression of ubiquitin-protein and ubiquitin-coding genes (UBA52, UBA80, UBB, UBC) in clinical tissues and cells.
- Performed overexpression and knockdown experiments of UBC and SEPT6 in DU145 prostate cancer cells.
- Utilized CCK-8, flow cytometry, and clonal formation assays to assess cell proliferation and cell cycle.
- Employed immunofluorescence for colocalization studies and Pearson correlation analysis for relationship assessment.
- Conducted tumor formation experiments to evaluate the in vivo effect of SEPT6/UBC.
Main Results:
- UBC expression was found to be upregulated in prostate cancer tissues and cells.
- Overexpression of UBC enhanced prostate cancer cell survival and proliferation.
- SEPT6 was identified as an upstream regulator of UBC, with SEPT6 inhibiting UBC expression.
- SEPT6 demonstrated an inhibitory effect on tumor growth in vivo.
- A negative correlation was observed between SEPT6 and UBC expression in prostate cancer tissues.
Conclusions:
- SEPT6 inhibits prostate cancer progression by suppressing UBC expression.
- This inhibition leads to reduced overall ubiquitination and affects the expression of downstream proliferation-related genes.
- SEPT6 acts as a tumor suppressor in prostate cancer, potentially through its regulation of UBC.
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