Identification of <i>G0S2</i> as a gene frequently methylated in squamous lung cancer by combination of <i>in silico</i> and experimental approaches

Kusakabe, Makoto; Kutomi, Tomoko; Watanabe, Kousuke; Emoto, Noriko; Aki, Naomi; Kage, Hidenori; Hamano, Emi; Kitagawa, Hiroshi; Nagase, Takahide; Sano, Atsushi; Yoshida, Yukihiro; Fukami, Takeshi; Murakawa, Tomohiro; Nakajima, Jun; Takamoto, Shinichi; Ota, Satoshi; Fukayama, Masashi; Yatomi, Yutaka; Ohishi, Nobuya; Takai, Daiya

doi:10.1002/ijc.24947

Cited by 50 publications

(38 citation statements)

References 45 publications

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“…7 Hypermethylation of the G0S2 promoter was found in primary head and neck squamous cell carcinoma, primary squamous lung cancer, and also in squamous lung cancer cell lines. [8][9][10] This epigenetic silencing of G0S2 in diverse types of cancer strengthens the case for G0S2 acting as a tumor suppressor. In vitro modification of G0S2 levels has shown little impact on cell growth, apoptosis or differentiation (unpublished data and Kusakabe et al).…”

Section: Introductionsupporting

confidence: 53%

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Mice lacking G0S2 are lean and cold-tolerant

Lopez‐Aguiar

et al. 2014

Cancer Biology & Therapy

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Section: Introductionsupporting

confidence: 53%

“…[7][8][9][10][16][17][18] However, its functions are still not well understood. To explore G0S2 function in vivo, G0S2 −/− mice were generated and characterized (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mice lacking G0S2 are lean and cold-tolerant

Lopez‐Aguiar

et al. 2014

Cancer Biology & Therapy

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“…Although several reports have indicated that CIMP is also distinguishable in NSCLC and is associated with a poor prognosis, (27,28) we have failed to distinguish the phenotype in the previous study regarding the methylation of the promoter regions of numerous protein-coding genes. (29) In the present study, we analyzed whether the concordant hypermethylation of multiple miRNA loci results in characteristics similar to those of CIMP. The methylated status of two or more miRNA loci was found to be associated with a significantly higher risk for advanced T status independent of age, sex, and smoking habit.…”

Section: Discussionmentioning

confidence: 99%

CpG island methylation of microRNAs is associated with tumor size and recurrence of non‐small‐cell lung cancer

Kitano

Watanabe²,

Emoto³

et al. 2011

Cancer Science

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We investigated whether the CpG island methylation of certain microRNAs was associated with the clinicopathological features and the prognosis of non-small-cell lung cancer. The methylation of mir-152, -9-3, -124-1, -124-2, and -124-3 was analyzed in 96 nonsmall-cell lung cancer specimens using a combined bisulfite restriction analysis. The median observation period was 49.5 months. The methylation of mir-9-3, -124-2, and -124-3 was individually associated with an advanced T factor independent of age, sex, and smoking habit. Moreover, the methylation of multiple microRNA loci was associated with a poorer progression-free survival in a univariate analysis. Our result enlightens the accumulation of aberrant DNA methylation which occurs in concordance with the tumor progression. (Cancer Sci 2011; 102: 2126-2131 L ung cancer is the leading cause of cancer-related mortality in the world,(1) and non-small-cell lung cancer (NSCLC) is the most common type. Surgical resection remains the only curative treatment for NSCLC. Identifying factors that are associated with aggressive disease may lead to the development of novel biomarkers and the identification of therapeutic targets that can help reduce the burden of this disease.MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate target gene expression by accelerating the degradation of mRNA and translational inhibition, with potentially hundreds of target mRNAs.(2) They influence a variety of cellular functions including proliferation, differentiation, and apoptosis.(3) Specific miRNAs can behave as either tumor suppressor genes or oncogenes, depending on the tissue type and the presence of specific targets. (4,5) More than 100 species of known miRNAs are embedded within or near the CpG islands of the human genome and are potentially subject to control by epigenetic alterations such as DNA methylation and histone modification. Systematic assessments of miRNA expression and epigenetic modifications among cell lines and primary tumor specimens have revealed the existence of the epigenetic regulation of miRNAs in multiple tumor types. (6)(7)(8)(9) The goals of this study were to explore possible relationships between the methylation profiles of miRNAs and the clinicopathological characteristics of NSCLC patients and to identify new specific methylation markers capable of detecting advanced pathological features.In the present study, the methylation status of five miRNA loci within five separate CpG islands was determined in 96 NSCLC tissue specimens. The choice of the miRNAs was based on our previous study (9) as well as other published reports. (10,11) Our data show that the CpG island methylation of miRNAs is common in NSCLC, and that the methylation of multiple miR-NA loci is associated with an advanced T status as well as the progression-free survival (PFS) of patients with NSCLC. Materials and MethodsPatients. We collected cancer tissues and normal lung tissues from NSCLC patients who underwent surgical resection at the University of Tokyo Hosp...

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“…These results also imply that p53 expression is not necessary for the antiproliferative effects of pioglitazone in NSCLC cells as H1299 cells do not express p53. G0S2 has been found to be frequently methylated in SCC of the lung (41), suggesting that G0S2 may have tumorsuppressive functions in the context of lung SCC. Additional mechanisms, such as induction of differentiation (24,25,27), inhibition of invasion, and inhibition of angiogenesis, may also be significant (23).…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive Effects of Pioglitazone on Chemically Induced Lung Carcinogenesis in Mice

Wang

James

Wang

et al. 2010

Molecular Cancer Therapeutics

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Pioglitazone [(RS)-5-(4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl)thiazolidine-2,4-dione] is a ligand of nuclear receptor peroxisome proliferator-activated receptor γ that is approved for the treatment of type II diabetes mellitus. Activation of peroxisome proliferator-activated receptor γ has been associated with anticancer activities in a variety of cancer cell lines through inhibition of proliferation and promotion of apoptosis. We examined the effect of pioglitazone on lung cancer development in carcinogen-induced lung adenocarcinoma and squamous cell carcinoma (SCC). When pioglitazone was administered beginning 8 weeks after the first carcinogen treatment when microscopic adenomas already existed, pioglitazone significantly inhibited tumor load (sum of tumor volume per lung in average) by 64% (P < 0.05) in p53 wt/wt mice and 50% (P < 0.05) in p53 wt/Ala135Val mice in the lung adenocarcinoma model. Delayed administration of pioglitazone caused a limited (35%, P < 0.05) decrease in lung SCC. Induction of apoptosis occurred in both model systems. These data show that pioglitazone significantly inhibited progression of both adenocarcinoma and SCC in the two mouse model systems. Mol Cancer Ther; 9(11); 3074-82. ©2010 AACR.

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Identification of G0S2 as a gene frequently methylated in squamous lung cancer by combination of in silico and experimental approaches

Cited by 50 publications

References 45 publications

Mice lacking G0S2 are lean and cold-tolerant

Mice lacking G0S2 are lean and cold-tolerant

CpG island methylation of microRNAs is associated with tumor size and recurrence of non‐small‐cell lung cancer

Chemopreventive Effects of Pioglitazone on Chemically Induced Lung Carcinogenesis in Mice

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