The role of hLHX6-HMR as a methylation biomarker for early diagnosis of cervical cancer
- Jung, Samil; Jeong, Dongjun; Kim, Jinsun; Yi, Lisha; Koo, Keunhoe; Lee, Jaehyouk; Lee, Soon-Duck; Park, Jin-Wha; Chang, Boogi; Kim, Chang-Hwan; Kim, Chang-Jin; Lee, Myeong-Sok
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- SPANDIDOS PUBL LTD
- epigenetics; mcthylation biomarker; cervical cancer; hLHX6-HMR
- ONCOLOGY REPORTS, v.23, no.6, pp.1675 - 1682
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- ONCOLOGY REPORTS
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- The homo sapiens LIM homeobox domain LHX6 gene, hLHX6, is a putative transcription regulator with homeodomain. Multiple cytosine guanine dinucleotides (CpG island) are found in the genomic sequences between exon 4a and exon 5 of the gene encoding hLHX6s (alternative short isoform of hLHX6 gene). This specific CpG island, hLHX6-HMR, is found frequently hypermethylated in 7 cervical cancer cell lines as shown in MSP, BSP, and COBRA assays. Methylation densities were also investigated with human tissue 'samples with a distinctive degree of malignant transformation. Our data showed that the hLHX6-HMR was rarely or partly methylated in the normal and CIN I cells, respectively. In contrast, it was frequently hypermethylated in CIN II, CIN III, and invasive carcinoma cells. In summary, this methylation study led to two conclusions. First, hLHX6-HMR hypermethylation is exclusively associated with cervical carcinogenesis. Second, the epigenetic change in hLHX6-HMR seems to start at CIN I, relatively early stage of cervical cancer development. Therefore, hLHX6-HMR can be used as an effective and sensitive methylation biomarker for early diagnosis of cervical cancer.
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