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circCRKL suppresses the progression of prostate cancer cells by regulating the miR-141/KLF5 axis
Cunjin Nan1, Yijun Wang1, Sen Yang1
1Department of Urology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China.
Background:
Prostate cancer (PCa) is a prevalent human malignancy in males. Circular RNA circCRKL (Hsa_circ_0001206) was reported to be lowly expressed in PCa tissues. However, the regulatory role of circCRKL in PCa is poorly defined.
Methods:
Levels of circCRKL, microRNA-141 (miR-141), and Kruppel-like factor (KLF5) were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell cycle progression, apoptosis, migration, and invasion were examined by Flow cytometry, Wound healing, and transwell assays. The underlying relationship between miR-141 and circCRKL or KLF5 was predicted by starBase, and then verified by a dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays. The protein level of KLF5 was assessed by western blot assay. The biological role of circCRKL was detected by a xenograft tumor model in vivo.
Results:
CircCRKL and KLF5 were decreased, and miR-141 was increased in PCa tissues and cells. The functional analysis discovered that the overexpression of circCRKL repressed cell cycle progression, migration, invasion, and boosted apoptosis of PCa cells. Mechanically, circCRKL could positively regulate KLF5 expression by sponging miR-141. In addition, circCRKL upregulation could hinder PCa tumor growth in vivo.
Conclusion:
These findings revealed that circCRKL inhibited the progression of PCa through upregulating KLF5 expression by sponging miR-141, elucidating a novel regulatory pathway in PCa cells. Our research suggested an underlying circRNA-targeted therapy for PCa.
Insights
Circular RNA circCRKL inhibits prostate cancer (PCa) progression by increasing KLF5 levels via sponging miR-141. This discovery offers a potential circRNA-targeted therapy for PCa patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer (PCa) is a common malignancy in men.
- Circular RNA circCRKL (Hsa_circ_0001206) expression is reduced in PCa.
- The specific role of circCRKL in PCa remains unclear.
Purpose of the Study:
- To investigate the regulatory role of circCRKL in prostate cancer.
- To elucidate the molecular mechanism underlying circCRKL's function in PCa.
- To explore circCRKL as a potential therapeutic target for PCa.
Main Methods:
- Quantitative PCR (RT-qPCR) to measure circCRKL, miR-141, and KLF5 levels.
- Cellular assays (flow cytometry, wound healing, Transwell) to assess proliferation, apoptosis, migration, and invasion.
- In vivo xenograft models to evaluate tumor growth inhibition.
Main Results:
- CircCRKL and KLF5 were downregulated, while miR-141 was upregulated in PCa tissues and cells.
- Overexpression of circCRKL suppressed PCa cell cycle progression, migration, and invasion, while promoting apoptosis.
- CircCRKL acts as a molecular sponge for miR-141, thereby upregulating KLF5 expression and inhibiting tumor growth in vivo.
Conclusions:
- CircCRKL inhibits PCa progression by upregulating KLF5 via sponging miR-141, revealing a novel regulatory pathway.
- These findings suggest circCRKL as a promising circRNA-based therapeutic strategy for prostate cancer.
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