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The mismatch repair gene hPMS1 (human postmeiotic segregation1) is down regulated in oral squamous cell carcinoma
Yimin Wang1, Xuanbo Zhou, Yang Song
1The Central Laboratory, China-Japan Union hospital, Jilin University, 126 Xiantai Street, Changchun, Jilin, 130033 China.
Abstract:
Genomic instability or microsatellite instability (MSI) was initially recognized in colonic carcinoma and subsequently in other tumors. MSI has been associated with mutations in genes that play a role in DNA replication and repair. In a previous study we detected MSI in 85% of young patients with OSCC and excluded the involvement of MMR genes hMLH1 and hMSH2. In the present study, we screened the mutation and expression status of the MMR genes hMSH3, hMSH6, hPMS1 and hPMS2 in OSCC and found expression of the hPMS1 protein to be down regulated. Genomic analysis of hPMS1 did not show any mutational changes in exonic or promoter regions. Expression of hPMS1 mRNA was not deregulated in either MSI positive or MSI negative tumor cell lines by Northern blot analysis. In contrast, analysis by Western blot showed that 100% of MSI positive tumor cell lines had decreased or no expression of hPMS1 while MSI negative cell lines had normal protein expression. Our data indicate that hPMS1 is most likely deregulated by post-transcriptional modification in OSCC while hMLH1 and hPMS2 has no detectable changes. Furthermore, our results are consistent with the hypothesis that hPMS1 is associated with MSI in OSCC.
Insights
Microsatellite instability (MSI) in oral squamous cell carcinoma (OSCC) is linked to the hPMS1 gene. This study found decreased hPMS1 protein expression in MSI-positive OSCC, suggesting post-transcriptional regulation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Genomic instability, specifically microsatellite instability (MSI), is observed in various cancers, including oral squamous cell carcinoma (OSCC).
- Previous research identified MSI in 85% of young OSCC patients but excluded involvement of mismatch repair (MMR) genes hMLH1 and hMSH2.
- The role of other MMR genes in OSCC-associated MSI requires further investigation.
Purpose of the Study:
- To investigate the mutation and expression status of MMR genes hMSH3, hMSH6, hPMS1, and hPMS2 in OSCC.
- To determine the specific mechanism of hPMS1 deregulation in OSCC.
- To assess the association between hPMS1 and MSI in OSCC.
Main Methods:
- Screening of mutation and expression of MMR genes (hMSH3, hMSH6, hPMS1, hPMS2) in OSCC.
- Genomic analysis of hPMS1 (exonic and promoter regions).
- Analysis of hPMS1 mRNA expression using Northern blot and protein expression using Western blot.
Main Results:
- Down-regulation of hPMS1 protein expression was observed in 100% of MSI-positive OSCC cell lines.
- No mutational changes were found in the exonic or promoter regions of hPMS1.
- hPMS1 mRNA expression was not deregulated, indicating post-transcriptional modification as the likely cause of protein down-regulation.
Conclusions:
- hPMS1 protein expression is significantly decreased or absent in MSI-positive OSCC.
- hPMS1 deregulation in OSCC appears to occur via post-transcriptional modification, not gene mutation.
- The findings support the hypothesis that hPMS1 is associated with MSI in oral squamous cell carcinoma.
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