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Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer
Zhenyu Song1, Zhiyuan Zhuo1, Zhe Ma1
1a Department of Urology, Jinshan Hospital of Fudan University , Shanghai , China.
Abstract:
Our study is to explore the expression profiles and potential functions of circRNAs in prostate cancer (PCa). A total of 95 circRNAs and 830 mRNAs were screened to be significantly differentially expressed in PCa tissues by microarrays. Co-expression and competitive endogenous RNA (ceRNA) network were constructed to reveal the potential regulatory mechanisms of circRNAs. Three circRNAs, hsa_circ_0001206, hsa_circ_0001633, and hsa_circ_0009061 were validated to be down-regulated in PCa by quantitative real-time PCR (qRT-PCR) and hsa_circ_0001206 as well as hsa_circ_0009061 was significantly associated with clinical features of PCa patients. Meanwhile, Receiver Operating Characteristic (ROC) curves showed their good diagnostic value as biomarkers for PCa. The down-regulation of hsa_circ_001206 was partly because of the regulation of DExH-Box Helicase 9 (DHX9). Moreover, overexpression of hsa_circ_0001206 inhibited PCa cell proliferation, migration, and invasion in vitro and prevented tumor growth in vivo. Dual-luciferase reporter assays showed hsa_circ_0001206 could directly bind to miR-1285-5p. The expression of Smad4, a well-known suppressive gene in PCa, can be increased by overexpression of hsa_circ_0001206 and this effect could be partly reversed by co-transfection of miR-1285-5p mimic. The study revealed expression profiles and potential functions of circRNAs and demonstrated hsa_circ_0001206 played a suppressive role in the pathogenesis of PCa.
Insights
This study identifies down-regulated circular RNAs (circRNAs) in prostate cancer (PCa), with hsa_circ_0001206 showing promise as a diagnostic biomarker and tumor suppressor. Further research confirmed its role in inhibiting PCa progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Prostate cancer (PCa) remains a significant health concern with a need for novel diagnostic and therapeutic targets.
- Circular RNAs (circRNAs) are emerging as key regulators in various cancers, including PCa, but their roles are not fully elucidated.
Purpose of the Study:
- To investigate the expression profiles and functional roles of circRNAs in prostate cancer.
- To identify potential circRNA biomarkers for PCa diagnosis and prognosis.
- To elucidate the regulatory mechanisms of circRNAs in PCa pathogenesis.
Main Methods:
- Microarray analysis to screen differentially expressed circRNAs and mRNAs in PCa tissues.
- Quantitative real-time PCR (qRT-PCR) for validation of circRNA expression.
- Co-expression and competitive endogenous RNA (ceRNA) network construction.
- In vitro and in vivo experiments to assess the functional impact of circRNAs.
- Dual-luciferase reporter assays to confirm direct interactions.
Main Results:
- 95 circRNAs and 830 mRNAs were found to be significantly differentially expressed in PCa.
- Three circRNAs (hsa_circ_0001206, hsa_circ_0001633, hsa_circ_0009061) were validated as down-regulated in PCa.
- hsa_circ_0001206 and hsa_circ_0009061 showed significant association with clinical features and good diagnostic value for PCa.
- Overexpression of hsa_circ_0001206 inhibited PCa cell proliferation, migration, invasion, and tumor growth.
- hsa_circ_0001206 directly targets miR-1285-5p and influences Smad4 expression.
Conclusions:
- circRNAs play crucial roles in the pathogenesis of prostate cancer.
- hsa_circ_0001206 acts as a tumor suppressor in PCa by regulating the miR-1285-5p/Smad4 axis.
- hsa_circ_0001206 holds potential as a diagnostic biomarker and therapeutic target for prostate cancer.
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