E2F2 serves as an essential prognostic biomarker and therapeutic target for human renal cell carcinoma by presenting "E2F2/miR-16-5p/SPTLC1" schema.
E2F2
Renal cell carcinoma
SPTLC1
miR-16–5p
Journal
Translational oncology
ISSN: 1936-5233
Titre abrégé: Transl Oncol
Pays: United States
ID NLM: 101472619
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
08
01
2023
revised:
18
05
2023
accepted:
22
05
2023
medline:
11
6
2023
pubmed:
11
6
2023
entrez:
10
6
2023
Statut:
ppublish
Résumé
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. 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. 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. E2F2 promoted RCC progression via the miR-16-5p/SPTLC1 axis, which may represent a novel prognostic and therapeutic biomarker for RCC.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
E2F2 promoted RCC progression via the miR-16-5p/SPTLC1 axis, which may represent a novel prognostic and therapeutic biomarker for RCC.
Identifiants
pubmed: 37300925
pii: S1936-5233(23)00085-2
doi: 10.1016/j.tranon.2023.101699
pmc: PMC10302538
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
101699Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no conflict of interest.
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