KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma

Guo, Zhongqiang; Liu, Jin; Su, Boxing; Xing, Yunchao; He, Qun; Ci, Weimin; Li, Xuesong; Zhou, Liqun

doi:10.1007/s13277-014-2746-7

Cited by 14 publications

(11 citation statements)

References 23 publications

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“…One of the kidney-specific genes, KCNJ1 (potassium channel, inwardly rectifying subfamily J, member 1), is required for maintaining potassium balance, which has recently been shown to have low-expression in tumor proliferation and metastasis. Additionally, it is an independent prognostic factor in clear cell renal cell carcinoma [26], which is in line with the observations in this study. In summary, the variety of the organ-specific genes in each organ is closely associated with organogenesis and/or organ-specific functions.…”

Section: Discussionsupporting

confidence: 91%

Pan-organ transcriptome variation across 21 cancer types

Yang

et al. 2016

Oncotarget

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It is widely accepted that some messenger RNAs are evolutionarily conserved across species, both in sequence and tissue-expression specificity. To date, however, little effort has been made to exploit the transcriptome divergence between cancer and adjacent normal tissue at the pan-organ level. In this work, a transcriptome sequencing dataset from 675 normal-tumor pairs, representing 21 solid organs in The Cancer Genome Atlas, is used to evaluate expression evolution. The results show that in most cancer types, gene expression divergence and organ-specificity are reduced in cancer tissue compared to adjacent normal tissue. Furthermore, we observe that all cancers share cell cycle dysregulation through interrogating differentially expressed protein coding genes. Meanwhile, weighted correlation network analysis is used to detect of the gene module structure variation between cancer and adjacent normal tissue. And modules consisting of tightly co-regulated genes in cancer change substantially compared with those in adjacent normal tissue. We thus assume that the destruction of a coordinated regulatory network might result in tumorigenesis and tumor progression. Our results provide new insights into the complex cancer biology and shed light on the mysterious regulation mode for cancer.

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Section: Discussionsupporting

confidence: 91%

Pan-organ transcriptome variation across 21 cancer types

Yang

et al. 2016

Oncotarget

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“…In addition, we identified several other genes that were hypermethylated and repressed that have been shown to suppress in vitro tumor phenotypes in RCC cells including PLXNB1, ATP1A, and KCNJ1 (33,35,37). Our study provides mechanistic insight into the silencing of these genes in kidney cancer.…”

Section: Discussionmentioning

confidence: 81%

“…We identified promoter hypermethylation and silencing of several genes previously reported to be reduced in RCC including ATP1A1 (ATPase Na þ /K þ transporting subunit alpha 1), ATP6V0A4 (ATPase Hþ transporting V0 subunit A4), KCNJ1 (potassium voltage-gated channel subfamily J member 1), CLCNKB (chloride voltage-gated channel Kb), PLXNB1 (plexin B1), and TMEM213 (transmembrane protein 213; refs. [33][34][35][36][37]. A novel finding was reduced expression of the gene encoding the estrogen receptor-related (ERR)-g (ESRRG).…”

Section: Characterization Of Genes Silenced In Rcc Via Promoter Methymentioning

confidence: 99%

Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis

Nam

Chandrashekar

Kundu

et al. 2019

Molecular Cancer Research

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The Cancer Genome Atlas (TCGA) and other large-scale genomic data pipelines have been integral to the current understanding of the molecular events underlying renal cell carcinoma (RCC). These data networks have focused mostly on primary RCC, which often demonstrates indolent behavior. However, metastatic disease is the major cause of mortality associated with RCC and data sets examining metastatic tumors are sparse. Therefore, a more comprehensive analysis of gene expression and DNA methylome profiling of metastatic RCC in addition to primary RCC and normal kidney was performed. Integrative analysis of the methylome and transcriptome identified over 30 RCC-specific genes whose mRNA expression inversely correlated with promoter methylation, including several known targets of hypoxia inducible factors. Notably, genes encoding several metabolism-related proteins were identified as differentially regulated via methylation including hexokinase 2, aldolase C, stearoyl-CoA desaturase, and estrogen-related receptor-γ (ESRRG), which has a known role in the regulation of nuclear-encoded mitochondrial metabolism genes. Several gene expression changes could portend prognosis in the TCGA cohort. Mechanistically, ESRRG loss occurs via DNA methylation and histone repressive silencing mediated by the polycomb repressor complex 2. Restoration of ESRRG in RCC lines suppresses migratory and invasive phenotypes independently of its canonical role in mitochondrial metabolism. Collectively, these data provide significant insight into the biology of aggressive RCC and demonstrate a novel role for DNA methylation in the promotion of HIF signaling and invasive phenotypes in renal cancer.

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“…On the other hand, we discovered an exclusive downregulation of KCNJ1. This gene is reported to inhibit proliferation and metastasis in renal cell carcinoma [37]. Currently, data of KCNJ1 for leukaemia is missing.…”

Section: Addition Of Idel To Arac Results In Pronounced Anti-prolifermentioning

confidence: 99%

“…In addition to the mentioned histones, both cell lines showed a specific pattern of the remaining combination specific top- 20 In SEM, Cytochrome P450 Family 3 Subfamily A Member 4 (CYP3A4 [35]; log fold-change − 4.11), Six Transmembrane Epithelial Antigen Of The Prostate 1 (STEAP1 [36]; log fold-change − 3.03) and Potassium Voltage-Gated Channel Subfamily J Member 1 (KCNJ1 [37]; log fold-change − 4.99) represents genes which were found only downregulated by the combination AraC + IDEL.…”

Section: Arac + Idel Modulates Histone Genes Predominantlymentioning

confidence: 99%

Combination of the PI3K inhibitor Idelalisib with the conventional cytostatics cytarabine and dexamethasone leads to changes in pathway activation that induce anti-proliferative effects in B lymphoblastic leukaemia cell lines

Sklarz¹,

Gladbach²,

Ernst³

et al. 2020

Cancer Cell Int

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Background: The introduction of combined conventional cytostatics and pathway-specific inhibitors has opened new treatment options for several cancer types including hematologic neoplasia such as leukaemias. As the detailed understanding of the combination-induced molecular effects is often lacking, the identification of combinationinduced molecular mechanisms bears significant value for the further development of interventional approaches. Methods: Combined application of conventional cytostatic agents (cytarabine and dexamethasone) with the PI3Kinhibitor Idelalisib was analysed on cell-biologic parameters in two acute pro-B lymphoblastic leukaemia (B-ALL) cell lines. In particular, for comparative characterisation of the molecular signatures induced by the combined and mono application, whole transcriptome sequencing was performed. Emphasis was placed on pathways and genes exclusively regulated by drug combinations. Results: Idelalisib + cytostatics combinations changed pathway activation for, e.g., "Retinoblastoma in cancer", "TGF-b signalling", "Cell cycle" and "DNA-damage response" to a greater extent than the two cytostatics alone. Analyses of the top-20 regulated genes revealed that both combinations induce characteristic gene expression changes. Conclusion: A specific set of genes was exclusively deregulated by the drug combinations, matching the combination-specific anti-proliferative cell-biologic effects. The addition of Idelalisib suggests minor synergistic effects which are rather to be classified as additive.

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KCNJ1 inhibits tumor proliferation and metastasis and is a prognostic factor in clear cell renal cell carcinoma

Cited by 14 publications

References 23 publications

Pan-organ transcriptome variation across 21 cancer types

Pan-organ transcriptome variation across 21 cancer types

Integrative Epigenetic and Gene Expression Analysis of Renal Tumor Progression to Metastasis

Combination of the PI3K inhibitor Idelalisib with the conventional cytostatics cytarabine and dexamethasone leads to changes in pathway activation that induce anti-proliferative effects in B lymphoblastic leukaemia cell lines

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