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Published on: March 30, 2019
circSOBP Inhibits Bladder Cancer Proliferation and Metastasis by Regulating the miR-200a-3p/PTEN Axis and
Yinglang Zhang1,2,3, Zhi Li1, Yu Zhang1,4
1Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Abstract:
A growing body of evidence shows that circular RNAs (circRNAs) participate in tumor growth and metastasis and also play crucial roles in the treatment and prognosis of various cancers. In this article, we identified a novel circRNA, circSOBP (has_circ_0001633), based on the results of high-throughput RNA sequencing, and its expression was subsequently validated via quantitative reverse transcription polymerase chain reaction in bladder cancer (BCa) tissues and cell lines. The association between circSOBP expression and the clinicopathologic features and prognosis of 56 recruited BCa patients was then analyzed, and the biological roles of circSOBP were assessed by in vitro cloning formation, wound healing, transwell, CCK-8, and in vivo xenograft mouse models. Next, the competitive endogenous RNA mechanism was explored through fluorescence in situ hybridization, RNA pull-down, luciferase reporter, bioinformatics analysis, and rescue experiments. Western blot and immunohistochemistry detected the expression of downstream mRNA, and we were able to determine that circSOBP was downregulated in BCa tissues and cell lines and that lower circSOBP expression was associated with more advanced pathological stage, larger tumor size, and poorer overall survival with BCa patients. Overexpressed circSOBP suppressed cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, competitive interactions between circSOBP and miR-200a-3p enhanced target gene PTEN expression. In addition, we found a significant correlation between higher expression of circSOBP in BCa patients after immunotherapy than before and a better treatment outcome, indicating that circSOBP might regulate the programmed death 1/programmed death ligand 1 pathway. Overall, circSOBP inhibits BCa tumorigenesis and metastasis by a novel miR-200a-3p/PTEN axis, which makes it an excellent biomarker and therapeutic target for treating BCa.
Insights
Circular RNAs (circRNAs) like circSOBP are crucial in bladder cancer (BCa). This study found circSOBP inhibits BCa growth and metastasis via the miR-200a-3p/PTEN pathway, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development and progression.
- Understanding specific circRNAs in bladder cancer (BCa) is vital for identifying new therapeutic targets and biomarkers.
Purpose of the Study:
- To identify and characterize a novel circRNA, circSOBP (has_circ_0001633), in bladder cancer.
- To investigate the role of circSOBP in BCa progression and its underlying molecular mechanisms.
- To evaluate circSOBP as a potential biomarker and therapeutic target for BCa.
Main Methods:
- High-throughput RNA sequencing and quantitative reverse transcription polymerase chain reaction (qRT-PCR) for circSOBP expression analysis.
- In vitro (cell proliferation, migration, invasion assays) and in vivo (xenograft mouse models) experiments to assess circSOBP's biological functions.
- Mechanistic studies including fluorescence in situ hybridization (FISH), RNA pull-down, luciferase reporter assays, and rescue experiments to elucidate the circRNA-miRNA-mRNA interactions.
- Western blot and immunohistochemistry to detect downstream protein expression.
- Correlation analysis with clinicopathologic features and patient survival data.
Main Results:
- circSOBP was found to be downregulated in BCa tissues and cell lines.
- Lower circSOBP expression correlated with advanced pathological stage, larger tumor size, and poorer patient survival.
- Overexpression of circSOBP suppressed BCa cell proliferation, migration, and invasion in vitro and in vivo.
- circSOBP acts as a competing endogenous RNA (ceRNA) by sponging miR-200a-3p, thereby enhancing PTEN expression.
- Increased circSOBP expression was observed after immunotherapy, suggesting a role in regulating the PD-1/PD-L1 pathway and potentially predicting treatment outcomes.
Conclusions:
- circSOBP inhibits bladder cancer tumorigenesis and metastasis through the novel miR-200a-3p/PTEN axis.
- circSOBP serves as a promising diagnostic biomarker and therapeutic target for bladder cancer.
- The findings suggest circSOBP's potential role in modulating the immune response in BCa patients undergoing immunotherapy.
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