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

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 0-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. Cancer Res; 78(24); 6771-84. Ó2018 AACR.

Lidocaine inhibits the progression of retinoblastoma in�vitro and in�vivo by modulating the miR‑520a‑3p/EGFR axis

“…It was recently reported that miR-520g was downregulated in esophageal cancer (16). Additionally, the miR-520 family is reported to have tumor suppressor roles in various human tumors, including breast (16) and renal and hepatocellular carcinoma (17,18). Previous studies have reported that miR-520a-3p was associated with the occurrence and development of numerous tumor types, such as colorectal and non-small cell lung cancer (19,20).…”

APPBP2 enhances non-small cell lung cancer proliferation and invasiveness through regulating PPM1D and SPOP

“…In renal cell carcinoma, SPOP can be activated by HIF and SPOP has very important oncogenic role suppressing PTEN and other genes, as well as activating AKT and ERK [43]. Consistently, researchers also found that SPOP, as a strong oncogenic protein, acted as a diagnostic biomarker in renal cell carcinoma [[44], [45], [46]]. Based on these reports, it is reasonable to hypothesize that APPBP2 enhances NSCLC proliferation and invasiveness partially through AR/CDK4/SPOP pathway (Fig.…”

The association of speckle-type POZ protein with lymph node metastasis and prognosis in cancer patients

“…Eventually, 9 studies were enrolled in the present meta-analysis, including 928 cases. [10–18] The main information obtained from the included studies was shown in Table 1. All studies included in the present meta-analysis were retrospective studies published between 2014 and 2018.…”

“…Multiple studies confirmed a significant correlation between decreased SPOP expression and poor prognosis in cancer patients, [10–15] while the opposite results were observed in other studies. [16–18] Since the prognostic relevance of SPOP expression in cancers remains controversial, it is essential to perform a meta-analysis to systematically evaluate the prognostic role of SPOP in cancer patients.…”