OncoTargets and Therapy (Oct 2019)
Hypermethylation Of ADHFE1 Promotes The Proliferation Of Colorectal Cancer Cell Via Modulating Cell Cycle Progression
Abstract
Yu-Han Hu,1,* Shuai Ma,1,* Xiang-Nan Zhang,2 Zhe-Ying Zhang,1 Hui-Fang Zhu,1,2 Ying-Hua Ji,3 Jian Li,4 Xin-Lai Qian,1,2 Yong-Xia Wang1,2 1Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, People’s Republic of China; 2Department of Pathology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, People’s Republic of China; 4Department of Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yong-Xia Wang; Xin-Lai QianDepartment of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453000, People’s Republic of ChinaTel +86-15090325842; +86-13839073820Email [email protected]; [email protected]: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Studies have demonstrated that epigenetic modifications play essential roles in the development of CRC. ADHFE1 is a differentially expressed gene that has been reported to be hypermethylated in CRC. However, the role and mechanism of ADHFE1 in the proliferation of CRC remain unclear.Materials and methods: ADHFE1 expression was analyzed in CRC tissues by IHC and qRT-PCR, and the relationship between ADHFE1 expression and the clinicopathological parameters was analyzed. Cell proliferation were assessed by the in vitro and in vivo experimental models. GSEA assay was performed to explore the mechanism of ADHFE1 in the proliferation of CRC. Flow cytometry and Western blot were used to detect the activation of the cell cycle signaling. Bisulfite genomic sequence (BSP) assay was used to test the methylation degree of ADHFE1 gene promoter in CRC tissues.Results: Here, we verified that ADHFE1 was down-regulated and hypermethylated in CRC tissues. The down-regulation of ADHFE1 was correlated with poor differentiation and advanced TNM stage of CRC patients. And ADHFE1 expression restored when the CRC cell line SW620 was treated with the demethylating agent 5-Aza-CdR. Overexpression of ADHFE1 inhibited the proliferation of CRC, while ADHFE1 knockdown promoted the proliferation of CRC cells in vitro and in vivo. Moreover, ADHFE1 overexpression could induce a significant G1-S cell cycle arrest in CRC cells and vice versa.Conclusion: Hypermethylation of ADHFE1 might promote cell proliferation by modulating cell cycle progression in CRC, potentially providing a new therapeutic target for CRC patients.Keywords: ADHFE1, colorectal cancer, hypermethylation, proliferation, cell cycle
