长链非编码 RNA FOXD2-AS1 通过 EZH2 表观遗传沉默 CDKN1B(p27) 在肝细胞癌中发挥致癌作用。
LncRNA FOXD2-AS1 plays an oncogenic role in hepatocellular carcinoma through epigenetically silencing CDKN1B(p27) via EZH2.
机构信息
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery First Affiliated Hospital, School of Medicine, Zhejiang University, PR China; NHFPC Key Laboratory of Combined Multi-organ Transplantation, PR China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, PR China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, PR China.
NHFPC Key Laboratory of Combined Multi-organ Transplantation, PR China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Chinese Academy of Medical Sciences, PR China; Key Laboratory of Organ Transplantation, Zhejiang Province, Hangzhou, PR China.
出版信息
Exp Cell Res. 2019 Jul 15;380(2):198-204. doi: 10.1016/j.yexcr.2019.04.016. Epub 2019 Apr 17.
Accumulating reports suggest that long noncoding RNAs (lncRNAs) play critical roles in the progression of many tumors. In this study, we explored the expression level of lncRNA FOXD2-AS1 in the tumorigenesis of hepatocellular carcinoma (HCC). The data indicated that FOXD2-AS1 expression was increased in HCC specimens and cell lines. Furthermore, aberrant expression was correlated with tumor number and tumor size in HCC patients. Silencing FOXD2-AS1 arrest cell cycle in the G0/G1 phase, inhibited colony formation, cell proliferation and suppressed the in vivo growth of subcutaneous tumors. Our results revealed that FOXD2-AS1 could epigenetically silence CDKN1B by recruiting EZH2 to CDKN1B promoter region. Knocking down CDKN1B could restore the carcinogenic effect of FOXD2-AS1 on HCC. Collectively, our data suggested that FOXD2-AS1 could be new target for therapies or prognostic biomarker in hepatocellular carcinoma.
越来越多的报告表明，长非编码 RNA（lncRNA）在许多肿瘤的进展中发挥着关键作用。在这项研究中，我们探讨了 lncRNA FOXD2-AS1 在肝细胞癌（HCC）发生中的表达水平。数据表明，lncRNA FOXD2-AS1 在 HCC 标本和细胞系中表达增加。此外，异常表达与 HCC 患者的肿瘤数量和肿瘤大小相关。沉默 FOXD2-AS1 可使细胞周期停滞在 G0/G1 期，抑制集落形成、细胞增殖，并抑制皮下肿瘤的体内生长。我们的结果表明，FOXD2-AS1 可以通过招募 EZH2 到 CDKN1B 启动子区域，表观遗传沉默 CDKN1B。敲低 CDKN1B 可以恢复 FOXD2-AS1 对 HCC 的致癌作用。总之，我们的数据表明，FOXD2-AS1 可能成为肝细胞癌治疗或预后的新靶点。
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