| Summary: | 碩士 === 輔仁大學 === 營養科學系碩士班 === 102 === Hedgehog (Hh) pathway increased tumor cells invasion and migration ability via regulates Epithelial-mesenchymal transition (EMT) and Hh signaling pathway is aberrantly activated in cancer. Folate status and genetic polymorphisms of one carbon enzyme: methylenetetrahydrofolate reductase (MTHFR) C677T and thymidylate synthase 5‘-untranslated region (TS5` UTR) polymorphism are associated with DNA promoter methylation. The aim of this study was to investigate the relationship among tumor folate status, genetic polymorphisms of one carbon enzyme, sonic hedgehog (Shh) signaling pathway molecules, invasion-associated biomarkers and colorectal cancer (CRC) progression. We collected 99 cancer tissues and pair-non cancer tissues of CRC in Tainan Chi Mei Medical Center. We used L. casei to analyze folate status, determining MTHFR C677T and TS5`UTR genotype by Q-PCR and the promoter methylation status of Shh by MS-PCR in tissues. In addition, using Q-RT-PCR analyze mRNA expression of Shh, Hedgehog-interacting protein (HIPP), glioma-associated oncogen homolog 1 (Gli1), β-catenin and E-cadherin. The folate status was significantly higher in T3 stage than T4 stage of the CRC tissue, but no relationship with genetic polymorphisms of MTHFR C677T and TS5`UTR. The genetic polymorphisms of MTHFR C677T and TS5`UTR were the same between CRC and non CRC tissue. Compared with MTHFR 677CC genotype, CT/TT genotype reduced the Shh overexpression in CRC tissue, but HHIP, E-cadherin and β-catenin mRNA expressions were no different in the CRC tissue and non CRC tissue.The mRNA expression of HHIP, E-cadherin and β-catenin were significantly lower in 3R/3R genotype than in 2R/2R+2R/3R genotype in the CRC tissue. The mRNA expression of Shh was overexpression and the mRNA expression of HHIP, E-cadherin and β-catenin were significantly decreased in early stage of metastasis in CRC tissue. In folate status and mRNA △△Ct expression of Shh, we found Shh expression and folate status were increased. Methylation of Shh promoter showed unrelated to folate status, genetic polymorphisms of one carbon enzyme and the mRNA expression of Shh. In conclusion, genetic polymorphisms of one carbon enzyme showed unrelated to folate status and the folate status was positive correlation with Shh mRNA expression. Shh pathway andEMT regulated early stage of CRC metastasis. The folate status and genetic polymorphisms of one carbon enzyme affected Shh pathway may not through hypermethylation of Shh promoter.
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