Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Sep;40(3):673-678.
doi: 10.3892/ijmm.2017.3044. Epub 2017 Jun 27.

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma

Haifeng Ni  1 , Bo Jiang  1 , Zhen Zhou  1 , Xiaoyang Yuan  1 , Xiaolin Cao  1 , Guangwu Huang  1 , Yong Li  1
Affiliations

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma

Haifeng Ni et al. Int J Mol Med. 2017 Sep.

Abstract

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation‑specific PCR, semi‑quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3‑methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.

PubMed Disclaimer

Figures

Figure 1
Figure 1
RT-PCR analysis of the mRNA expression of MutS homolog human 3 (MSH3), and the mRNA expression levels of MSH3 in nasopharyngeal carcinoma (NPC) biopsies (i.e., T1, T2, and T3) and normal nasopharyngeal epithelial (i.e., N1, N2, and N3) samples. The data are representative of 2 independent experiments. In addition, β-actin, normal colorectal tissue and water were used as an internal control, positive controls (PC) and blank control, respectively.
Figure 2
Figure 2
Immunohistochemical staining of the protein expression of MutS homolog human 3 (MSH3) in normal nasopharyngeal epithelial (NNE) tissues and primary nasopharyngeal carcinoma (NPC) biopsy specimens. (A and B) Represent examples of NNE and NPC, respectively.
Figure 3
Figure 3
Methylation-specific PCR analysis of the MutS homolog human 3 (MSH3) promoter region in nasopharyngeal carcinoma biopsies (i.e., T1, T2, and T3) and normal nasopharyngeal primary epithelial (i.e., N1, N2, and N3) samples. The data are representative of 2 independent experiments. In vitro methylated DNA was used as a methylation-positive control and DNA from normal lymphocytes was used as an unmethylated positive control. Water was included as a blank control. M, methylated alleles; U, unmethylated alleles; PC, positive control.
Figure 4
Figure 4
The mRNA expression level of MutS homolog human 3 (MSH3) in methylated nasopharyngeal carcinoma (NPC) tissues and unmethylated NPC tissues.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Tao Q, Chan AT. Nasopharyngeal carcinoma: molecular pathogenesis and therapeutic developments. Expert Rev Mol Med. 2007;9:1–24. doi: 10.1017/S1462399407000312. - DOI - PubMed
    1. Lung HL, Cheung AK, Ko JM, Cheng Y, Stanbridge EJ, Lung ML. Deciphering the molecular genetic basis of NPC through functional approaches. Semin Cancer Biol. 2012;22:87–95. doi: 10.1016/j.semcancer.2011.11.002. - DOI - PubMed
    1. Lo KW, Chung GT, To KF. Deciphering the molecular genetic basis of NPC through molecular, cytogenetic, and epigenetic approaches. Semin Cancer Biol. 2012;22:79–86. doi: 10.1016/j.semcancer.2011.12.011. - DOI - PubMed
    1. Fishel R. The selection for mismatch repair defects in hereditary nonpolyposis colorectal cancer: revising the mutator hypothesis. Cancer Res. 2001;61:7369–7374. - PubMed
    1. Jensen LE, Jauert PA, Kirkpatrick DT. The large loop repair and mismatch repair pathways of Saccharomyces cerevisiae act on distinct substrates during meiosis. Genetics. 2005;170:1033–1043. doi: 10.1534/genetics.104.033670. - DOI - PMC - PubMed

MeSH terms