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Updated: Sep 30, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Circular RNA circDVL1 inhibits clear cell renal cell carcinoma progression through the miR-412-3p/PCDH7 axis
Ying Wang1,2, Yunjing Zhang1,2, Xinwan Su3
1The Fourth Affiliated Hospital, and International Institutes of Medicine, Zhejiang University School of Medicine, Jinhua 322000, Zhejiang, China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) is a primary kidney cancer with high aggressive phenotype and extremely poor prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) play pivotal roles in the occurrence and development of various human cancers. However, the expression, clinical significance and regulatory role of circRNAs in ccRCC remain largely unclear. Here we report that circDVL1 to be reduced in the serums and tissues from ccRCC patients, and to negatively correlate with ccRCC malignant features. Overexpression of circDVL1 inhibits proliferation, induces G1/S arrest, triggers apoptosis, and reduces migration and invasion in different ccRCC cells in vitro. Correspondingly, circDVL1 overexpression suppresses ccRCC tumorigenicity in a mouse xenograft model. Mechanistically, circDVL1 serves as a sponge for oncogenic miR-412-3p, thereby preventing miR-412-3p-mediated repression of its target protocadherin 7 (PCDH7) in ccRCC cells. Collectively, our results demonstrate that circDVL1 exerts tumor-suppressive function during ccRCC progression through circDVL1/miR-412-3p/PCDH7 axis, and suggest that circDVL1 could be a novel diagnostic and prognositc marker and therapeutic target for ccRCC.
Insights
Circular RNA DVL1 (circDVL1) is decreased in clear cell renal cell carcinoma (ccRCC). Restoring circDVL1 inhibits ccRCC progression and tumor growth, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is an aggressive kidney cancer with poor prognosis.
- Circular RNAs (circRNAs) are implicated in various cancers, but their role in ccRCC is not well understood.
Purpose of the Study:
- To investigate the expression, clinical significance, and regulatory role of circRNAs in ccRCC.
- To explore circDVL1 as a potential biomarker and therapeutic target for ccRCC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) to measure circRNA expression in ccRCC tissues and serums.
- Cell proliferation, apoptosis, migration, and invasion assays in ccRCC cell lines.
- In vivo tumor xenograft assays in a mouse model.
- Mechanism studies involving circRNA-RNA interactions (e.g., miRNA sponging).
Main Results:
- circDVL1 expression is significantly reduced in ccRCC tissues and serums and correlates negatively with tumor malignancy.
- Overexpression of circDVL1 inhibits ccRCC cell proliferation, induces cell cycle arrest, promotes apoptosis, and reduces migration and invasion.
- circDVL1 overexpression suppresses ccRCC tumor growth in vivo.
- circDVL1 acts as a molecular sponge for miR-412-3p, relieving the repression of its target gene PCDH7.
Conclusions:
- circDVL1 functions as a tumor suppressor in ccRCC progression via the circDVL1/miR-412-3p/PCDH7 axis.
- circDVL1 holds promise as a diagnostic and prognostic marker for ccRCC.
- circDVL1 represents a potential therapeutic target for ccRCC treatment.
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