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.

Abstract	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.
Authors	Michael Friedrich, Nadine Heimer, Christine Stoehr, André Steven, Sven Wach, Helge Taubert, Arndt Hartmann, Barbara Seliger
Journal	Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 6499 (04 16 2020) ISSN: 2045-2322 [Electronic] England
PMID	32300145 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
Chemical References	CREB1 protein, human Cyclic AMP Response Element-Binding Protein MicroRNAs
Topics	Adult Aged Aged, 80 and over Carcinoma, Renal Cell (genetics, pathology, surgery) 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, surgery) Kidney Neoplasms (genetics, pathology, surgery) Male MicroRNAs (metabolism) Middle Aged Neoplasm Grading Neoplasm Invasiveness (genetics) Neoplasm Staging Nephrectomy Tissue Array Analysis Up-Regulation

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