In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 24 ( 2018-12-15), p. 6771-6784
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.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/0008-5472.CAN-18-1662
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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