Neuroglobin and myoglobin in non-small cell lung cancer: Expression, regulation and prognosis

Oleksiewicz, Urszula; Daskoulidou, Nikoleta; Liloglou, Triantafillos; Tasopoulou, Kalliopi-Maria; Bryan, Julie; Gosney, John R.; Field, John K.; Xinarianos, George

doi:10.1016/j.lungcan.2011.05.001

Cited by 53 publications

(70 citation statements)

References 43 publications

(82 reference statements)

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“…For instance, Galluzzo et al (33) demonstrated that overexpression of MB in non-small-cell lung cancer cells suppressed the hypoxia response, inhibited tumor growth, reduced vessel density, promoted tumor differentiation and suppressed tumor metastasis. On the other hand, Oleksiewicz et al (13) reported that patients with non-small-cell lung cancer with low MB levels had a longer survival duration than patients with high MB expression. Hypoxia may also induce the expression of MB in prostate cancer (11) and renal cell carcinoma (12).…”

Section: Discussionmentioning

confidence: 99%

“…Myoglobin (MB) is an oxygen-binding respiratory protein that has been identified in various non-muscle tissues (8). Previous studies have revealed that mRNA and/or protein levels of MB may be induced by hypoxia and were correlated with the expression of numerous hypoxia biomarkers, including HIF-1α, HIF-2α, and carbonic anhydrase IX (CAIX) in various types of cancer (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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Influence of hypoxia‑related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF

et al. 2017

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Abstract. Tumor hypoxia is common in a number of solid tumor types including gastric cancer, and is associated with treatment resistance and poor prognosis. The present study aimed to investigate the function of hypoxia-associated genetic polymorphisms in predicting treatment response and survival in patients with metastatic gastric cancer (MGC) treated with EOF (oxaliplatin and 5-fluorouracil combined with epirubicin) as first-line chemotherapy. The present retrospective study enrolled 108 Chinese patients with MGC receiving EOF as first-line chemotherapy, and genotyped six single nucleotide polymorphisms (SNPs) in four hypoxia-associated genes [myoglobin (MB) rs7292 and rs7293, ATP Binding Cassette Subfamily G Member 2 rs2231142, MutL homolog 1 (MLH1) rs1800734 and rs9852810, and Poly(ADP-Ribose) Polymerase 1 rs1136410]. The results of the present study indicated that the CT/TT genotype of MB rs7292, as well as the GG genotype of MLH1 rs9852810, were independent favorable predictive factors of progression-free survival [PFS; MB rs7292: hazard ratio (HR)=0.135, 95% confidence interval (CI)=0.057-0.321, P<0.001; MLH1 rs9852810: HR=0.494, 95% CI=0.267-0.913, P=0.024). Using a prognostic index based on the favorable SNPs for PFS (MB rs7292 CT/TT genotype, and MLH1 rs9852810 GG genotype), patients were classified into a low-risk group (involving one or two of the two SNPs) and a high-risk group (involving neither of the two SNPs), with a PFS of 180.0 and 117.0 days, respectively (P=0.002). The results of the present study demonstrated that the CT/TT genotype of MB rs7292 and the GG genotype of MLH1 rs9852810 were independent favorable predictive factors of PFS in patients with MGC treated with EOF. Identification of those SNPs in blood samples may allow for the prediction of the short-term efficacy of first-line EOF treatment in patients with MGC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Influence of hypoxia‑related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF

et al. 2017

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“…However, Gorr et al (2011) reports that neither Ngb nor Cygb is systematically up-regulated in tumors. In non-small cell lung cancer, the down-regulation of Ngb is found to be associated with Ngb promoter hypermethylation (Oleksiewicz et al, 2011). Hypermethylation of Cygb promoter has also been found in several tumors (Shivapurkar et al, 2008).…”

Section: Introductionmentioning

confidence: 98%

“…Emara et al (2010) reports that Ngb and cytoglobin (Cygb) are detected in most types of tumors by microarray analysis. Oleksiewicz et al (2011) reports that Ngb is significantly up-regulated in lung cancer. However, Gorr et al (2011) reports that neither Ngb nor Cygb is systematically up-regulated in tumors.…”

Section: Introductionmentioning

confidence: 99%

Neuroglobin, a Novel Intracellular Hexa-Coordinated Globin, Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Raf/MAPK/Erk

et al. 2013

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Hypoxia and oxidative stress are critical factors in carcinogenesis and exist throughout cancer development; however, the underlying mechanisms are far from clear. Here, for the first time to our knowledge, we reported that neuroglobin (Ngb), an intracellular hexa-coordinated globin serving as an oxygen/ reactive oxygen species (ROS) sensor, functions as a tumor suppressor in hepatocelluar carcinoma (HCC). Ngb protein and mRNA expression were significantly down-regulated in tumor tissues, compared with its adjacent non-tumor tissues of human HCC samples and normal liver tissues. Knock-down of Ngb by RNA interference promoted human HCC cell line (HepG2) growth and proliferation, G0/G1-S transition in vitro, and tumor growth in vivo. On the contrary, overexpression of Ngb suppressed HepG2 cell growth and proliferation, G0/G1-S transition, colony formation in vitro, and tumorigenicity in vivo. These results established a tumor suppressor function of Ngb in HCC.The underlying mechanisms were further investigated. Overexpression of Ngb suppressed Raf/MEK/extracellular signalregulated kinase (Erk), whereas knockdown of Ngb enhanced Raf/MEK/Erk activation in HepG2 cells in vitro and in vivo. Glutathione S-transferase pull-down showed that Ngb interacted with c-Raf-1 in HepG2 cells. Overexpression of Ngb suppressed serum-and H 2 O 2 -stimulated Erk activation in HepG2 cells. Pharmacological inhibition of Erk activation abolished the proliferative effect of Ngb knockdown in HepG2 cells. Mutation of Ngb at its oxygen-binding site (H64L) abolished the inhibitory effects of Ngb on Erk activation and HepG2 cell proliferation. Therefore, we propose that Ngb controls HCC development by linking oxygen/ROS signals to oncogenic Raf/mitogen-activated protein kinase (MAPK)/Erk signaling. Our data suggest that neuroglobin could be a new target for cancer therapy.

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“…particularly in various epithelial tumours and cancer cell lines (10)(11)(12)(13)(14). So far, the biological function and pathophysiological role of ectopically expressed MB is poorly understood.…”

mentioning

confidence: 99%

Ectopic Myoglobin Expression Is Associated with a Favourable Outcome in Head and Neck Squamous Cell Carcinoma Patients

Meller

Ellen

Gevensleben

et al. 2016

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Abstract. Background/Aim: Ectopic myoglobin (MB)expressionMyoglobin (MB) is a cytoplasmatic monomeric oxygenbinding hemoprotein known to be localized mainly in cardiac myocytes and mitochondrial-rich skeletal muscles. In contrast to its relative haemoglobin, MB is only found in the blood stream after muscle injury. The functional paradigm of MB is the storage and intracellular transport of oxygen (O 2 ) (1, 2) to the mitochondria for oxidative phosphorylation within the myocyte. However, MB also maintains homeostasis of the nitric oxide free radical (NO•) in muscle through scavenging or producing NO• molecules (3, 4) and appropriating excessive reactive oxygen species (ROS) (5). In addition, MB is able to bind fatty acids with physiological binding constants in vitro (6). On the other hand, MB-knockout mice are viable and exhibit normal exercise capacity but their survival depends on the activation of compensating mechanisms, i.e. increasing capillary densities and haematocrit (7,8).In the last years, the existence of non-muscle MB has been increasingly acknowledged, demonstrating MB, e.g., in the liver, brain or gills of carps (9) and in humans, 6235

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Neuroglobin and myoglobin in non-small cell lung cancer: Expression, regulation and prognosis

Cited by 53 publications

References 43 publications

Influence of hypoxia‑related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF

Influence of hypoxia‑related genetic polymorphisms on the prognosis of patients with metastatic gastric cancer treated with EOF

Neuroglobin, a Novel Intracellular Hexa-Coordinated Globin, Functions as a Tumor Suppressor in Hepatocellular Carcinoma via Raf/MAPK/Erk

Ectopic Myoglobin Expression Is Associated with a Favourable Outcome in Head and Neck Squamous Cell Carcinoma Patients

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