KLF6 depletion promotes NF-κB signaling in glioblastoma

Masilamani, Anie P.; Ferrarese, Roberto; Kling, Eva; Thudi, Nanda K.; Kim, Hoon; Scholtens, Denise M.; Dai, Fangping; Hadler, Michael; Unterkircher, Thomas; Platania, Leonardo; Weyerbrock, Astrid; Prinz, Marco; Gillespie, G. Yancey; Harsh, Griffith R.; Bredel, Markus; Carro, Maria Stella

doi:10.1038/onc.2016.507

Cited by 32 publications

(28 citation statements)

References 61 publications

(82 reference statements)

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“…The only potential tumor suppressor gene being hypermethylated was KLF6 . KLF6 depletion was associated with various cancers and a potential role in SI-NET warrants further investigation 24 – 27 . Unfortunately, since only FFPE tissue was available, no analysis of KLF6-expression could be performed within this study.…”

Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors

Walter

Harter

Battke

et al. 2018

Sci Rep

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Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary and metastatic lesions as well as benign liver of five patients with synchronously metastasized, well differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue. Thereby, 156 single nucleotide variants (SNVs) in 150 genes were identified and amount of mutations per sample ranged from 9–34 (mean 22). The degree of common (0–94%) and private mutations per sample was strongly varying (6–100%). In all patients, copy number variations (CNV) were found and the degree of intratumoral heterogeneity of CNVs corresponded to SNV analysis. DNA methylation analysis of a patient without common SNVs revealed a large overlap of common methylated CpG sites. In conclusion, SI-NET primary and metastatic lesions show a highly varying degree of intratumoral heterogeneity. Driver events might not be detectable with exome analysis only, and further comprehensive studies including whole genome and epigenetic analyses are warranted.

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Section: Discussionmentioning

confidence: 99%

Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors

Walter

Harter

Battke

et al. 2018

Sci Rep

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“… UN 64 NEFM KLF6 inhibits the malignant phenotype of GBM in vitro and upregulates neuronal marker NEFM. UP 65 SYNPR SYNPR is downregulated differently expressed genes (DEGs) in GBM tissue samples. Down 66 TMEM130 UN UN GABRA1 Upregulation of miR-155 in GBM could may downregulate GABRA1 which renders tumor cells unresponsive to GABA signaling.…”

Section: Resultsmentioning

confidence: 99%

Genome-wide expression profiling of glioblastoma using a large combined cohort

Tang

Yang

et al. 2018

Sci Rep

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Glioblastomas (GBMs), are the most common intrinsic brain tumors in adults and are almost universally fatal. Despite the progresses made in surgery, chemotherapy, and radiation over the past decades, the prognosis of patients with GBM remained poor and the average survival time of patients suffering from GBM was still short. Discovering robust gene signatures toward better understanding of the complex molecular mechanisms leading to GBM is an important prerequisite to the identification of novel and more effective therapeutic strategies. Herein, a comprehensive study of genome-scale mRNA expression data by combining GBM and normal tissue samples from 48 studies was performed. The 147 robust gene signatures were identified to be significantly differential expression between GBM and normal samples, among which 100 (68%) genes were reported to be closely associated with GBM in previous publications. Moreover, function annotation analysis based on these 147 robust DEGs showed certain deregulated gene expression programs (e.g., cell cycle, immune response and p53 signaling pathway) were associated with GBM development, and PPI network analysis revealed three novel hub genes (RFC4, ZWINT and TYMS) play important role in GBM development. Furthermore, survival analysis based on the TCGA GBM data demonstrated 38 robust DEGs significantly affect the prognosis of GBM in OS (p < 0.05). These findings provided new insights into molecular mechanisms underlying GBM and suggested the 38 robust DEGs could be potential targets for the diagnosis and treatment.

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“…Krüppel‐like factor 6 ( KLF6 ), also known as Core promoter element‐binding (COPEB) protein, is a common nuclear transcription factor in mammalian cells that was originally cloned from human placenta tissue and rat liver star mesenchyme . Recent studies showed that KLF6 is deregulated in cancers such as glioblastoma, prostate cancer, hepatocellular carcinomas, and colorectal cancer . KLF6 has important roles in regulating multiple biological processes including cell cycle, apoptosis, and differentiation regulation in cancer cells .…”

Section: Discussionmentioning

confidence: 99%

Coexpression network analysis identified Krüppel‐like factor 6 (KLF6) association with chemosensitivity in ovarian cancer

Chen

et al. 2018

J of Cellular Biochemistry

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Although most patients with ovarian cancer (OC) are initially sensitive to paclitaxel/carboplatin combination chemotherapy, eventually they develop resistance to chemotherapy drugs and experience disease relapse. OC is the most lethal gynecological malignancy, and the five-year survival rate is extremely low. Thus, research on specific biomarkers and potential targets for chemotherapy-resistant patients with OC is needed. In our study, genes in the top 10% of variance in data set GSE30161 from chemoresistant and chemosensitive OC tissues were determined to conduct a weighted gene coexpression network analysis (WGCNA). The magenta module was most strongly related to OC chemoresponse. Gene ontology enrichment analysis indicated that the function of the magenta module primarily focused on transcription regulation, cell cycle control, and apoptosis modulation. Integration of the WGCN with the protein-protein interaction network identified five candidate genes. These five genes were verified using the GSE51373 test set, and Krüppel-like factor 6 ( KLF6) was identified as tightly linked to OC chemosensitivity. The receiver operating characteristic (ROC) curve showed that KLF6 differentiated chemoresistant from chemosensitive OC tissues. The Kaplan-Meier online database indicated that high KLF6 expression was associated with poor OC prognosis. Gene set enrichment analysis determined that the KLF6 mechanism was potentially associated with cell cycle, mTOR, and DNA-damage repair signaling pathways. In conclusion, KLF6 was identified in association with OC chemoresistance, and the mechanism of KLF6-mediated chemoresistance may involve the cell cycle, mTOR, and DNA-damage repair signaling pathways.

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KLF6 depletion promotes NF-κB signaling in glioblastoma

Cited by 32 publications

References 61 publications

Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors

Genetic heterogeneity of primary lesion and metastasis in small intestine neuroendocrine tumors

Genome-wide expression profiling of glioblastoma using a large combined cohort

Coexpression network analysis identified Krüppel‐like factor 6 (KLF6) association with chemosensitivity in ovarian cancer

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