Aberrant upregulation of ASCL2 by promoter demethylation promotes the growth and resistance to 5-fluorouracil of gastric cancer cells
Oh-Hyung Kwon
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Search for more papers by this authorJong-Lyul Park
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Search for more papers by this authorSu-Jin Baek
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Search for more papers by this authorSeung-Moo Noh
Department of General Surgery, College of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorKyu-Sang Song
Department of Pathology, Chungnam National University, Daejeon, Korea
Search for more papers by this authorCorresponding Author
Seon-Young Kim
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
To whom correspondence should be addressed.
E-mails: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Yong Sung Kim
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
To whom correspondence should be addressed.
E-mails: [email protected]; [email protected]
Search for more papers by this authorOh-Hyung Kwon
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Search for more papers by this authorJong-Lyul Park
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Search for more papers by this authorSu-Jin Baek
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Search for more papers by this authorSeung-Moo Noh
Department of General Surgery, College of Medicine, Chungnam National University, Daejeon, Korea
Search for more papers by this authorKyu-Sang Song
Department of Pathology, Chungnam National University, Daejeon, Korea
Search for more papers by this authorCorresponding Author
Seon-Young Kim
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
To whom correspondence should be addressed.
E-mails: [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Yong Sung Kim
Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Department of Functional Genomics, University of Science and Technology, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
To whom correspondence should be addressed.
E-mails: [email protected]; [email protected]
Search for more papers by this authorAbstract
Achaete scute-like 2 (ASCL2), a basic helix-loop-helix transcription factor, plays an essential role in the maintenance of adult intestinal stem cells. However, the function of ASCL2 in gastric cancer (GC) is poorly understood. Therefore, we investigated the roles and regulatory transcription mechanisms of ASCL2 in GC. Gene expression and methylation data analysis showed that ASCL2 was upregulated and hypomethylated in GC tissues. Using real-time RT-PCR and pyrosequencing analysis, we confirmed that ASCL2 was overexpressed and hypomethylated in GC tissues compared to adjacent normal tissues. We then investigated the mechanisms underlying the aberrant expression of ASCL2 in GC and found that treatment with a methylation inhibitor induced ASCL2 expression in GC cell lines. MBD-sequencing assay also revealed hypermethylation of the promoter region of ASCL2 in GC cell lines, which barely expressed the ASCL2 gene. Furthermore, ASCL2 expression levels were inversely correlated with GC patient survival. Ectopic overexpression of ASCL2 showed that ASCL2 increased cell growth and promoted resistance to 5-fluorouracil in GC cells. These results suggest that ASCL2 might play an important role in gastric tumor growth and chemoresistance, and could be a useful prognostic marker for GC patients.
Supporting Information
| Filename | Description |
|---|---|
| cas12076-sup-0001-FigS1.docWord document, 190 KB | Fig. S1. The expression and methylation level of ASCL2 in gastric normal and cancer tissues. |
| cas12076-sup-0002-DocS1.docWord document, 32 KB | Doc. S1. Material and methods details. |
| cas12076-sup-0003-TableS1.docWord document, 40.5 KB | Table S1. Primer information. |
| cas12076-sup-0004-TableS2.docWord document, 45 KB | Table S2. ASCL2 expression in tumors with respect to clinicopathologic characteristics. |
| cas12076-sup-0005-TableS3.docWord document, 45 KB | Table S3. ASCL2 methylation in tumors with respect to clinicopathologic characteristics. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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