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Published on: May 21, 2019
circCEP128 Knockdown Suppresses Bladder Cancer Progression via Regulating microRNA-515-5p/SDC1 Axis
Guanghui Cao1, Chan Zhang1, Xiangyong Tian1
1Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, Henan, 450003, People's Republic of China.
Background:
Dysregulation of circular RNAs (circRNAs) is associated with bladder cancer progression. Nevertheless, the mechanisms of circRNA centrosomal protein 128 (circCEP128) underlying bladder cancer progression remain poorly understood.
Methods:
The levels of circCEP128, microRNA-515-5p (miR-515-5p) and syndecan-1 (SDC1) were determined via reverse transcription-quantitative polymerase chain reaction or Western blot. The effects of circCEP128, miR-515-5p and SDC1 on bladder cancer progression were investigated via MTT and colony formation assays, flow cytometry and transwell analysis and subcutaneous xenograft experiments. The interactions between miR-515-5p and circCEP128 or SDC1 were examined through bioinformatics prediction and luciferase reporter assay.
Results:
circCEP128 and SDC1 were highly expressed and miR-515-5p was low expressed in bladder cancer tissues and cells. circCEP128 knockdown hindered cell proliferation, migration and invasion and promoted cell apoptosis in bladder cancer. circCEP128 loss increased miR-515-5p expression through direct interaction in bladder cancer cells. MiR-515-5p depletion mitigated the influences of circCEP128 knockdown on bladder cancer cell phenotypes. SDC1 was a direct target of miR-515-5p. circCEP128 positively regulated SDC1 expression via miR-515-5p. MiR-515-5p restrained the malignant progression of bladder cancer cells by decreasing SDC1 expression. circCEP128 knockdown hindered the growth of bladder cancer xenograft tumors by up-regulating miR-515-5p and down-regulating SDC1.
Conclusion:
circCEP128 knockdown hampered the tumorigenesis and progression of bladder cancer by regulating miR-515-5p/SDC1 axis in vitro and in vivo, deepening our understanding on the molecular mechanisms of circCEP128 in bladder cancer.
Insights
Circular RNA circCEP128 promotes bladder cancer by upregulating SDC1 via the miR-515-5p pathway. Silencing circCEP128 inhibits tumor growth and progression, offering a potential therapeutic target for bladder cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
- Dysregulation of circRNAs is implicated in bladder cancer progression.
- The specific mechanisms of circRNA centrosomal protein 128 (circCEP128) in bladder cancer remain largely unknown.
Purpose of the Study:
- To elucidate the role and molecular mechanisms of circCEP128 in bladder cancer progression.
- To investigate the regulatory relationship between circCEP128, microRNA-515-5p (miR-515-5p), and syndecan-1 (SDC1) in bladder cancer.
Main Methods:
- Quantitative reverse transcription PCR and Western blotting were used to measure gene and protein expression levels.
- Cell proliferation, migration, invasion, and apoptosis were assessed using MTT, colony formation, flow cytometry, and Transwell assays.
- In vivo tumor growth was evaluated through subcutaneous xenograft experiments in mice.
- Molecular interactions were confirmed using bioinformatics predictions and luciferase reporter assays.
Main Results:
- circCEP128 and SDC1 were significantly upregulated, while miR-515-5p was downregulated in bladder cancer tissues and cells.
- Knockdown of circCEP128 suppressed bladder cancer cell proliferation, migration, and invasion, while promoting apoptosis.
- circCEP128 positively regulated SDC1 expression by sponging miR-515-5p, and miR-515-5p inhibited bladder cancer progression by targeting SDC1.
- circCEP128 knockdown inhibited tumor growth in vivo by upregulating miR-515-5p and downregulating SDC1.
Conclusions:
- circCEP128 knockdown effectively inhibits bladder cancer tumorigenesis and progression both in vitro and in vivo.
- The circCEP128/miR-515-5p/SDC1 axis plays a critical role in bladder cancer development.
- These findings provide a deeper understanding of circCEP128's molecular mechanisms in bladder cancer and suggest its potential as a therapeutic target.
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