E2F2 serves as an essential prognostic biomarker and therapeutic target for human renal cell carcinoma by presenting “E2F2/miR-16–5p/SPTLC1” schema

Abstract

Background: Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with high mortality and morbidity. Although E2F2, a classical transcription factor implicated in cell cycle, has been shown to foster tumorigenesis in several human cancers, it could not draw a satisfy answer referring to precise downstream signaling axis in RCC development yet. Methods: Based on the publicly available data from TCGA database, expression patterns of E2F2, SPTLC1 and miR-16–5p were identified, either with the ability to predict the prognosis of patients with RCC, which was further validated in 38 paired RCC tissues and matched adjacent tissues by RT-qPCR and Western blot, respectively. Their cellular biofunctions were evaluated using MTT, EdU, Colony formation and transwell assays. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay were employed to certain the exquisite core transcription regulatory circuitry of E2F2/miR-16–5p/SPTLC1 in RCC progression, which was also determined in xenograft tumor model. Results: Consistent with the public TCGA database, E2F2 was significantly increased in RCC tissues and cells, indicating shorter overall survival. Mechanistically, E2F2 served as a transcriptional activator of miR-16–5p, thus accounting for its negative regulation on SPTLC1 expression. E2F2 knockdown-mediated suppressive biofunctions on RCC cells were rescued by miR-16–5p mimics, while this effect was abolished again by SPTLC1 overexpression. Role of E2F2 on RCC tumorigenesis via the miR-16–5p/SPTLC1 axis was verified both in vitro and in vivo. Conclusion: E2F2 promoted RCC progression via the miR-16–5p/SPTLC1 axis, which may represent a novel prognostic and therapeutic biomarker for RCC.

Keywords

• E2F2
• Renal cell carcinoma
• miR-16–5p
• SPTLC1