NFκB mediated elevation of KCNJ11 promotes tumor progression of hepatocellular carcinoma through interaction of lactate dehydrogenase A

Zhang, Ke; Mu, Lina; Ding, Mingcui; Xu, Rui; Ding, Zhaojun; Liang, Jun

doi:10.1016/j.bbrc.2017.11.011

Cited by 19 publications

(15 citation statements)

References 24 publications

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“…GSE62043, GSE14520, and GSE6764 are the Gene Expression Omnibus accession numbers for related studies. The upregulation of KCNJ11 (Zhang et al, 2018) and the downregulation of catalase (Cho et al, 2014), PXR , or cytidine deaminase (Nwosu et al, 2017) in HCC have been recently reported. KCNJ11 is an HCC oncogene and its overexpression in HCC promotes cell proliferation and tumor progression (Zhang et al, 2018).…”

Section: Phase I Enzymementioning

confidence: 91%

Deregulation of the Genes that Are Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Hepatocellular Carcinoma

Marri

Mackenzie

et al. 2019

The Journal of Pharmacology and Experimental Therapeutics

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Genes involved in drug absorption, distribution, metabolism, and excretion (ADME) are called ADME genes. Currently, 298 genes that encode phase I and II drug metabolizing enzymes, transporters, and modifiers are designated as ADME genes by the PharmaADME Consortium. ADME genes are highly expressed in the liver and their levels can be influenced by liver diseases such as hepatocellular carcinoma (HCC). In this study, we obtained RNA-sequencing and microRNA (miRNA)-sequencing data from 371 HCC patients via The Cancer Genome Atlas liver hepatocellular carcinoma project and performed ADME gene-targeted differential gene expression analysis and expression correlation analysis. Two hundred thirty-three of the 298 ADME genes (78%) were expressed in HCC. Of these genes, almost one-quarter (58 genes) were significantly downregulated, while only 6% (15) were upregulated in HCC relative to healthy liver. Moreover, one-half (14/28

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Section: Phase I Enzymementioning

confidence: 91%

Deregulation of the Genes that Are Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Hepatocellular Carcinoma

Marri

Mackenzie

et al. 2019

The Journal of Pharmacology and Experimental Therapeutics

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“…In the glycolytic pathway, lactate dehydrogenase A (LDHA) irreversibly catalyzes the conversion of pyruvate to lactate via the oxidative dehydrogenation of nicotinamide adenine dinucleotide (NADH) to NAD+. Several studies have reported that LDHA is highly expressed in various cancers such as pancreatic cancer, gastric, gallbladder, and breast cancers, as well as nasopharyngeal and hepatocellular carcinomas; its expression is positively correlated with the malignant progression of the cancers (9)(10)(11)(12)(13)(14)(15). However, the relationship between LDHA expression and the progression of OSCC, as well as the underlying mechanisms that affect the biological behavior of OSCC cells, are still unclear.…”

Section: Introductionmentioning

confidence: 99%

LDHA Promotes Oral Squamous Cell Carcinoma Progression Through Facilitating Glycolysis and Epithelial–Mesenchymal Transition

Cai

Zhang

et al. 2019

Front. Oncol.

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Aerobic glycolysis is the main pathway for energy metabolism in cancer cells. It provides energy and biosynthetic substances for tumor progression and metastasis by increasing lactate production. Lactate dehydrogenase A (LDHA) promotes glycolysis process by catalyzing the conversion of pyruvate to lactate. Despite LDHA exhibiting carcinogenesis in various cancers, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study demonstrated that LDHA was over-expressed in both OSCC tissues and cell lines, and was significantly associated with lower overall survival rates in patients with OSCC. Using weighted gene correlation network analysis and gene set enrichment analysis for the gene expression data of patients with OSCC (obtained from The Cancer Genome Atlas database), a close association was identified between epithelial-mesenchymal transition (EMT) and LDHA in promoting OSCC progression. The knockdown of LDHA suppressed EMT, cell proliferation, and migration and invasion of OSCC cells in vitro. Moreover, the silencing of LDHA inhibited tumor growth in vivo. Oxamate, as a competitive LDHA inhibitor, was also suppressed diverse malignant biocharacteristics of OSCC cells. Our findings reveal that LDHA acts as an oncogene to promote malignant progression of OSCC by facilitating glycolysis and EMT, and LDHA may be a potential anticancer therapeutic target.

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“…1 KCNJ11 acts as an oncogene in HCC by forming a complex with lactate dehydrogenase A (LDHA). 9 Abnormal Na + and Cl − channels also contribute to hallmarks of cancers. 1 However, whether or not the alterations in ion channels result in abnormal ion levels in cancer cells compared to their adjacent normal counterparts remains to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Systematic analysis of concentrations of 52 elements in tumor and counterpart normal tissues of patients with non‐small cell lung cancer

Cheng

Zhou

et al. 2019

Cancer Medicine

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Background Many studies have documented the abnormal concentrations of major/trace elements in serum or malignant tissues of patients, but very few works systematically tested the concentrations of elements in tumor tissues in comparison with paired adjacent normal tissues from the same patients. Methods Tumor and adjacent normal lung tissues were obtained from 93 patients with previously untreated NSCLC, and 43 patients whose tumor and paired normal lung tissues reached 200 mg or more were selected for measurement of the elements' concentrations using an inductively coupled plasma‐atomic emission spectrometer. Results We found that the concentrations of the 52 elements varied from 0.4 ng/g tissue (Lu, Pd, and Tm) to 1 658 000 ng/g (Na), 1 951 000 ng/g (P), and 2 495 000 ng/g (K). Thirty eight of the 52 (73.1%) elements showed approximately equal concentrations in tumor and adjacent normal lung tissues of the patients. The concentrations of nine elements (K, P, Mg, Zn, Rb, Cu, Se, Cs, and Tl) in tumor samples were significantly higher than their paired normal lung tissues, and five elements (Na, Fe, Cr, Cd, and Ge) exhibited decreased concentrations in cancer samples compared to counterpart normal lung tissues. Low Fe in tumor samples was associated with smoking history, whereas low Cr was associated with histology (squamous cell carcinoma) of the patients. Conclusions Our results demonstrate that measurement of elements’ concentrations in both cancer and paired normal tissues is important to get insights into the roles of these elements in carcinogenesis, and therapeutic approaches to normalize the elements are warranted to treat NSCLCs.

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NFκB mediated elevation of KCNJ11 promotes tumor progression of hepatocellular carcinoma through interaction of lactate dehydrogenase A

Cited by 19 publications

References 24 publications

Deregulation of the Genes that Are Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Hepatocellular Carcinoma

Deregulation of the Genes that Are Involved in Drug Absorption, Distribution, Metabolism, and Excretion in Hepatocellular Carcinoma

LDHA Promotes Oral Squamous Cell Carcinoma Progression Through Facilitating Glycolysis and Epithelial–Mesenchymal Transition

Systematic analysis of concentrations of 52 elements in tumor and counterpart normal tissues of patients with non‐small cell lung cancer

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