Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
Department of Bio and Chemical Engineering, Hongik University, Sejong, Republic of Korea.
Sci Rep. 2017 Jun 12;7(1):3274. doi: 10.1038/s41598-017-03639-3.
Recently, the roles of FAM83H in tumorigenesis have been interested and increased expression of FAM83H and MYC in hepatocellular carcinoma (HCC) have been reported. Therefore, we investigated the expression and role of FAM83H in 163 human HCCs and further investigated the relationship between FAM83H and oncogene MYC. The expression of FAM83H is elevated in liver cancer cells, and nuclear expression of FAM83H predicted shorter survival of HCC patients. In HLE and HepG2 HCC cells, knock-down of FAM83H inhibited proliferation and invasive activity of HCC cells. FAM83H induced expression of cyclin-D1, cyclin-E1, snail and MMP2 and inhibited the expression of P53 and P27. In hepatic tumor cells derived from Tet-O-MYC mice, the expression of mRNA and protein of FAM83H were dependent on MYC expression. Moreover, a chromatin immunoprecipitation assay demonstrated that MYC binds to the promotor of FAM83H and that MYC promotes the transcription of FAM83H, which was supported by the results of a dual-luciferase reporter assay. In conclusion, we present an oncogenic role of FAM83H in liver cancer, which is closely associated with the oncogene MYC. In addition, our results suggest FAM83H expression as a poor prognostic indicator of HCC patients.
最近，人们对 FAM83H 在肿瘤发生中的作用产生了兴趣，并报道了 FAM83H 和 MYC 在肝细胞癌（HCC）中的高表达。因此，我们研究了 FAM83H 在 163 个人 HCC 中的表达和作用，并进一步研究了 FAM83H 与癌基因 MYC 之间的关系。FAM83H 在肝癌细胞中的表达升高，FAM83H 的核表达预测 HCC 患者的生存时间更短。在 HLE 和 HepG2 HCC 细胞中，敲低 FAM83H 抑制了 HCC 细胞的增殖和侵袭活性。FAM83H 诱导了细胞周期蛋白 D1、E1、snail 和 MMP2 的表达，并抑制了 P53 和 P27 的表达。在 Tet-O-MYC 小鼠来源的肝肿瘤细胞中，FAM83H 的 mRNA 和蛋白表达依赖于 MYC 的表达。此外，染色质免疫沉淀分析表明，MYC 结合 FAM83H 的启动子，并且 MYC 促进 FAM83H 的转录，双荧光素酶报告基因分析的结果支持了这一结果。总之，我们提出了 FAM83H 在肝癌中的致癌作用，它与癌基因 MYC 密切相关。此外，我们的结果表明 FAM83H 表达是 HCC 患者预后不良的指标。
