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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 27 - 34 (8page)
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Purpose: Ovarian cancer (OC) is the most fatal of gynecological malignancies with a high rate of recurrence. We aimed to evaluatethe expression of solute carrier family 6, member 12 (SLC6A12) and methylation of its promoter CpG sites in a xenograft mousemodel of metastatic OC, and to investigate the regulatory mechanisms that promote aggressive properties during OC progression.
Materials and Methods: Expression of SLC6A12 mRNA was determined by reverse-transcription quantitative polymerase chainreaction (RT-qPCR), and DNA methylation status of its promoter CpGs was detected by quantitative methylation-specific PCR. Themetastatic potential of SLC6A12 was evaluated by in vitro migration/invasion transwell assays. Gene expression and DNA methylationof SLC6A12 and clinical outcomes were further investigated from publicly available databases from curatedOvarianDataand The Cancer Genome Atlas.
Results: SLC6A12 expression was 8.1–14.0-fold upregulated and its DNA methylation of promoter CpG sites was 41–62% decreasedin tumor metastases. After treatment with DNA methyltransferase inhibitor and/or histone deacetylase inhibitor, the expression ofSLC6A12 was profoundly enhanced (~8.0-fold), strongly supporting DNA methylation-dependent epigenetic regulation of SLC6A12.
Overexpression of SLC6A12 led to increased migration and invasion of ovarian carcinoma cells in vitro, approximately 2.0-fold and3.3-fold, respectively. The meta-analysis showed that high expression of SLC6A12 was significantly associated with poor overall survival[hazard ratio (HR)=1.07, p value=0.016] and that low DNA methylation levels of SLC6A12 at specific promoter CpG site negativelyaffected patient survival.
Conclusion: Our findings provide novel evidence for the biological and clinical significance of SLC6A12 as a metastasis-promotinggene.
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참고문헌 (17)
참고문헌 신청
American Cancer Society / 2015 / Cancer facts & figures 2015 / American Cancer Society
Lengyel E / 2010 / Ovarian cancer development and metastasis / Am J Pathol 177:1053~1064
Asadollahi R / 2010 / Epigenetics of ovarian cancer:from the lab to the clinic / Gynecol Oncol 118:81~87
Balch C / 2009 / Minireview:epigenetic changes in ovarian cancer / Endocrinology 150:4003~4011
Zhou Y / 2012 / The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface / Am J Physiol Renal Physiol 302:F316~F328
Lengyel E / 2010 / Ovarian cancer development and metastasis / Am J Pathol 177:1053~1064
Asadollahi R / 2010 / Epigenetics of ovarian cancer:from the lab to the clinic / Gynecol Oncol 118:81~87
Balch C / 2009 / Minireview:epigenetic changes in ovarian cancer / Endocrinology 150:4003~4011
Zhou Y / 2012 / The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface / Am J Physiol Renal Physiol 302:F316~F328
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