TY  - JOUR
A1  - Kotlyar, Mischa J.
A1  - Krebs, Markus
A1  - Solimando, Antonio Giovanni
A1  - Marquardt, André
A1  - Burger, Maximilian
A1  - Kübler, Hubert
A1  - Bargou, Ralf
A1  - Kneitz, Susanne
A1  - Otto, Wolfgang
A1  - Breyer, Johannes
A1  - Vergho, Daniel C.
A1  - Kneitz, Burkhard
A1  - Kalogirou, Charis
T1  - Critical evaluation of a microRNA-based risk classifier predicting cancer-specific survival in renal cell carcinoma with tumor thrombus of the inferior vena cava
JF  - Cancers
N2  - (1) Background: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCC\(^{IVC}\)) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier — containing miR-21-5p, miR-126-3p and miR-221-3p expression — which significantly predicted the cancer-specific survival (CSS) of ccRCC\(^{IVC}\) patients. (2) Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCC\(^{IVC}\), we measured the expression levels of miR-21, miR-126, and miR-221 using qRT-PCR. The prognostic impact of clinicopathological parameters and miR expression were investigated via single-variable and multivariable Cox regression. Referring to the previously established risk classifier, we performed Kaplan–Meier analyses for single miR expression levels and the combined risk classifier. Cut-off values and weights within the risk classifier were taken from the previous study. (3) Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at the time of surgery, the development of metastasis during follow-up, and cancer-related death. In Kaplan–Meier analyses, miR-21 and miR-126 significantly impacted CSS in our cohort. Moreover, applying the miR-based risk classifier significantly stratified ccRCC\(^{IVC}\) according to CSS. (4) Conclusions: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCC\(^{IVC}\) cohort.
KW  - kidney cancer
KW  - RCC
KW  - venous infiltration
KW  - biomarker
KW  - miR
KW  - risk stratification
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311040
SN  - 2072-6694
VL  - 15
IS  - 7
ER  - 
TY  - JOUR
A1  - Fetiva, Maria Camila
A1  - Liss, Franziska
A1  - Gertzmann, Dörthe
A1  - Thomas, Julius
A1  - Gantert, Benedikt
A1  - Vogl, Magdalena
A1  - Sira, Nataliia
A1  - Weinstock, Grit
A1  - Kneitz, Susanne
A1  - Ade, Carsten P.
A1  - Gaubatz, Stefan
T1  - Oncogenic YAP mediates changes in chromatin accessibility and activity that drive cell cycle gene expression and cell migration
JF  - Nucleic Acids Research
N2  - YAP, the key protein effector of the Hippo pathway, is a transcriptional co-activator that controls the expression of cell cycle genes, promotes cell growth and proliferation and regulates organ size. YAP modulates gene transcription by binding to distal enhancers, but the mechanisms of gene regulation by YAP-bound enhancers remain poorly understood. Here we show that constitutive active YAP5SA leads to widespread changes in chromatin accessibility in untransformed MCF10A cells. Newly accessible regions include YAP-bound enhancers that mediate activation of cycle genes regulated by the Myb-MuvB (MMB) complex. By CRISPR-interference we identify a role for YAP-bound enhancers in phosphorylation of Pol II at Ser5 at MMB-regulated promoters, extending previously published studies that suggested YAP primarily regulates the pause-release step and transcriptional elongation. YAP5SA also leads to less accessible ‘closed’ chromatin regions, which are not directly YAP-bound but which contain binding motifs for the p53 family of transcription factors. Diminished accessibility at these regions is, at least in part, a consequence of reduced expression and chromatin-binding of the p53 family member ΔNp63 resulting in downregulation of ΔNp63-target genes and promoting YAP-mediated cell migration. In summary, our studies uncover changes in chromatin accessibility and activity that contribute to the oncogenic activities of YAP.
KW  - oncogenic YAP
KW  - chromatin
KW  - cell cycle
KW  - gene expression
KW  - cell migration
KW  - YAP5SA
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350218
VL  - 51
IS  - 9
ER  -