CREB1 is affected by the microRNAs miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p and correlates with adverse clinicopathological features in renal cell carcinoma.
Adult
Aged
Aged, 80 and over
Carcinoma, Renal Cell
/ genetics
Cell Line, Tumor
Computational Biology
Cyclic AMP Response Element-Binding Protein
/ genetics
Down-Regulation
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
HEK293 Cells
Humans
Kidney
/ pathology
Kidney Neoplasms
/ genetics
Male
MicroRNAs
/ metabolism
Middle Aged
Neoplasm Grading
Neoplasm Invasiveness
/ genetics
Neoplasm Staging
Nephrectomy
Tissue Array Analysis
Up-Regulation
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 04 2020
16 04 2020
Historique:
received:
28
10
2019
accepted:
11
03
2020
entrez:
18
4
2020
pubmed:
18
4
2020
medline:
15
12
2020
Statut:
epublish
Résumé
The transcription factor cAMP response element-binding protein (CREB1) has been shown to be involved in diverse biological pathways including the regulation of cell proliferation, apoptosis, cell cycle progression, and metastasis. In this context, aberrant expression of CREB1 and the functional consequences are well investigated in a number of hematopoietic and solid tumors. However, CREB1 expression and underlying control mechanisms are only poorly analyzed in renal cell carcinoma (RCC). The present study confirmed a deregulation of CREB1 protein in the clear cell type of RCC (ccRCC) and analysis of in-house ccRCC cell lines suggested a post-transcriptional control. The combination of miRNA enrichment assay, in silico analysis and molecular biological approaches revealed four novel CREB1-regulating miRNAs, namely miR-22-3p, miR-26a-5p, miR-27a-3p, and miR-221-3p. Categorizing RCC samples as CREB1 negative or positive, respectively, the expression of these miRNAs was found to be inversely correlated with CREB1 protein levels. Analyzing 453 consecutive RCC tumors by immunohistochemistry, weakly negative, but significant correlations of CREB1 with tumor stage and grade, vascular invasion (V1) and lymphovascular invasion (L1) were found. In this respect, ccRCC might differ from other solid tumors like esophageal squamous-cell carcinoma or glioma.
Identifiants
pubmed: 32300145
doi: 10.1038/s41598-020-63403-y
pii: 10.1038/s41598-020-63403-y
pmc: PMC7162877
doi:
Substances chimiques
CREB1 protein, human
0
Cyclic AMP Response Element-Binding Protein
0
MicroRNAs
0
Types de publication
Journal Article
Observational Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6499Références
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