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长链非编码RNA AFAP1-AS1通过锌指增强子同源物2促进结直肠癌肿瘤生长。

Long noncoding RNA AFAP1-AS1 facilitates tumor growth through enhancer of zeste homolog 2 in colorectal cancer.

作者信息

Tang Jianming, Zhong Guansheng, Wu Jianhui, Chen Haiyan, Jia Yongshi

机构信息

Department of Radiation Oncology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College Hangzhou 310009, Zhejiang, P. R. China.

Department of Thyroid and Breast Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College Hangzhou 310009, Zhejiang, P. R. China.

出版信息

Am J Cancer Res. 2018 May 1;8(5):892-902. eCollection 2018.

Abstract

Increasing evidences have shown that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. However, the contributions of lncRNAs to colorectal cancer remain largely unknown. Here, we identify a lncRNA AFAP1-AS1 that facilitates colorectal cancer, where it is upregulated. AFAP1-AS1 expression was associated with colorectal cancer patient survival. AFAP1-AS1 knockdown inhibited cell proliferation, cell cycle, and tumorigenesis in an subcutaneous mouse xenograft model system. Further data demonstrated that AFAP1-AS1 was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. Our findings indicate that AFAP1-AS1 is an oncogenic lncRNA that promotes tumor progression and may be a novel prognostic factor in colorectal cancer. Targeting AFAP1-AS1 might be a potential therapeutic strategy for colorectal cancer treatment.

摘要

越来越多的证据表明,长链非编码RNA(lncRNA)在癌症生物学中发挥着关键的调控作用。然而,lncRNA对结直肠癌的作用在很大程度上仍不清楚。在此,我们鉴定出一种促进结直肠癌的lncRNA AFAP1-AS1,其在结直肠癌中表达上调。AFAP1-AS1的表达与结直肠癌患者的生存率相关。在皮下小鼠异种移植模型系统中,敲低AFAP1-AS1可抑制细胞增殖、细胞周期及肿瘤发生。进一步的数据表明,AFAP1-AS1与zeste同源物2增强子(EZH2)相关,且这种关联是抑制EZH2靶基因所必需的。我们的研究结果表明,AFAP1-AS1是一种致癌lncRNA,可促进肿瘤进展,可能是结直肠癌的一种新型预后因子。靶向AFAP1-AS1可能是结直肠癌治疗的一种潜在治疗策略。

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