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The E2F1-miR-520/372/373-SPOP Axis Modulates Progression of Renal Carcinoma

The E2F1-miR-520/372/373-SPOP Axis Modulates Progression of Renal Carcinoma

Meng Ding, Xiaolan Lu, Cheng Wang, Quan Zhao, Jingping Ge, Qiuyuan Xia, Junjun Wang, Ke Zen, Chen-Yu Zhang, Chunni Zhang

Cancer Res. 2018 Dec 15;78(24):6771-6784.

PMID: 30348808

Abstract:

: Although renal cell carcinoma (RCC) is the most malignant urologic cancer, its pathogenesis remains unclear, and effective treatments for advanced RCC are still lacking. Here, we report that a novel E2F1-miR-520/372/373-SPOP axis controls RCC carcinogenesis. Speckle-type POZ protein (SPOP) was upregulated in over 90% of RCC tissues, whereas the miR-520/372/373 family was downregulated and correlated inversely with SPOP protein levels in RCC tissues. The miR-520/372/373 family targeted the SPOP 3'-UTR and suppressed SPOP protein expression, leading to elevation of PTEN and DUSP7 levels and, consequently, decreased proliferation, invasion/migration, and metastasis of RCC cells in vitro and in vivo. Tail-vein delivery of therapeutic miR-520/372/373 family significantly decreased both tumor size and lung metastasis ratio in mice bearing orthotopic xenograft tumors. Decreased expression of miR-520/372/373 family was mediated by transcription factor E2F1. In conclusion, our results demonstrate that the E2F1-miR-520/372/373-SPOP axis functions as a key signaling pathway in RCC progression and metastasis and represents a promising opportunity for targeted therapies. SIGNIFICANCE: These findings show that the E2F1-miR-520/372/373 family-SPOP axis promotes RCC progression, thereby contributing to our understanding of RCC pathogenesis and unveiling new avenues for more effective targeted therapies.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR424667	Phalloidin-Atto 520			Price

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