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Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.

Shi M, Wang S, Yao Y, Li Y, Zhang H, Han F, Nie H, Su J, Wang Z, Yue L, Cao J, Li Y - Sci Rep (2014)

Bottom Line: Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers.The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA).The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

ABSTRACT
Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significance of MARVELD1 gene silencing in lung cancer. Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers. DNA hypermethylation and histone deacetylation synergistically inactivated MARVELD1 gene in lung cancer cells. Moreover, MARVELD1 modulated the efficiency of nonsense-mediated mRNA decay (NMD) through interaction with NMD core factor SMG1. The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA). The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis.

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Related in: MedlinePlus

Effect of epigenetic inhibitors on expression of MARVELD1 gene in lung cancer cells.(a), (c) Western blotting analysis showed the effect of 5-aza-CdR (a) and the effect of 5-aza-CdR and TSA (c) on MARVELD1 expression in A549 cells. Full length blots were shown in supplementary figure 6b, 6c. (b), (d) Relative intensities of bands in western blotting were determined by using NIH image software.
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f3: Effect of epigenetic inhibitors on expression of MARVELD1 gene in lung cancer cells.(a), (c) Western blotting analysis showed the effect of 5-aza-CdR (a) and the effect of 5-aza-CdR and TSA (c) on MARVELD1 expression in A549 cells. Full length blots were shown in supplementary figure 6b, 6c. (b), (d) Relative intensities of bands in western blotting were determined by using NIH image software.

Mentions: DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine (5-aza-CdR) can reverse the abnormal CpG islands hypermethylation and recover the expression of the silenced tumor suppressor genes. Therefore, we investigated the influence of 5-aza-CdR on the expression of MARVELD1 gene in lung cancer cells. MARVELD1 expression was obviously enhanced by 5 μM of 5-aza-CdR in A549 cells in a time-dependent manner. H520 with high MARVELD1 expression acted as a positive control (Figure 3a). MARVELD1 level in 5-aza-CdR treated A549 cells was significantly increased during 24 to 72 h of treatment as compared with untreated group. 72 h of 5-aza-CdR treatment induced more MARVELD1 expression than shorter incubation period (24 and 48 h) (Figure 3b). We also detected MARVELD1 expression in different concentration of 5-aza-CdR, and found an apparent dose-dependent increase of MARVELD1 level (Figure S3).


Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.

Shi M, Wang S, Yao Y, Li Y, Zhang H, Han F, Nie H, Su J, Wang Z, Yue L, Cao J, Li Y - Sci Rep (2014)

Effect of epigenetic inhibitors on expression of MARVELD1 gene in lung cancer cells.(a), (c) Western blotting analysis showed the effect of 5-aza-CdR (a) and the effect of 5-aza-CdR and TSA (c) on MARVELD1 expression in A549 cells. Full length blots were shown in supplementary figure 6b, 6c. (b), (d) Relative intensities of bands in western blotting were determined by using NIH image software.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4269892&req=5

f3: Effect of epigenetic inhibitors on expression of MARVELD1 gene in lung cancer cells.(a), (c) Western blotting analysis showed the effect of 5-aza-CdR (a) and the effect of 5-aza-CdR and TSA (c) on MARVELD1 expression in A549 cells. Full length blots were shown in supplementary figure 6b, 6c. (b), (d) Relative intensities of bands in western blotting were determined by using NIH image software.
Mentions: DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine (5-aza-CdR) can reverse the abnormal CpG islands hypermethylation and recover the expression of the silenced tumor suppressor genes. Therefore, we investigated the influence of 5-aza-CdR on the expression of MARVELD1 gene in lung cancer cells. MARVELD1 expression was obviously enhanced by 5 μM of 5-aza-CdR in A549 cells in a time-dependent manner. H520 with high MARVELD1 expression acted as a positive control (Figure 3a). MARVELD1 level in 5-aza-CdR treated A549 cells was significantly increased during 24 to 72 h of treatment as compared with untreated group. 72 h of 5-aza-CdR treatment induced more MARVELD1 expression than shorter incubation period (24 and 48 h) (Figure 3b). We also detected MARVELD1 expression in different concentration of 5-aza-CdR, and found an apparent dose-dependent increase of MARVELD1 level (Figure S3).

Bottom Line: Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers.The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA).The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

ABSTRACT
Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significance of MARVELD1 gene silencing in lung cancer. Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers. DNA hypermethylation and histone deacetylation synergistically inactivated MARVELD1 gene in lung cancer cells. Moreover, MARVELD1 modulated the efficiency of nonsense-mediated mRNA decay (NMD) through interaction with NMD core factor SMG1. The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA). The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis.

Show MeSH
Related in: MedlinePlus