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长链非编码RNA CRNDE通过表观遗传沉默DUSP5/CDKN1A表达促进结肠癌细胞增殖。

Long noncoding RNA CRNDE promotes colorectal cancer cell proliferation via epigenetically silencing DUSP5/CDKN1A expression.

作者信息

Ding Jie, Li Juan, Wang HaiYan, Tian Yun, Xie Min, He XueZhi, Ji Hao, Ma Zhonghua, Hui Bingqing, Wang Keming, Ji Guozhong

机构信息

Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

Department of Ultrasonography, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

出版信息

Cell Death Dis. 2017 Aug 10;8(8):e2997. doi: 10.1038/cddis.2017.328.

Abstract

Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes. In addition, the knockdown of CRNDE significantly suppressed proliferation and caused apoptosis of CRC cells both in vitro and in vivo. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that lncRNA CRNDE could epigenetically suppress the expressions of dual-specificity phosphatase 5 (DUSP5) and CDKN1A by binding to EZH2 (the key components of Polycomb repressive complex 2 (PRC2)), thus promoting CRC development. In conclusion, our data suggest that the lncRNA CRNDE promotes the progression of CRC and is a potential therapeutic target for CRC intervention.

摘要

证据表明,长链非编码RNA(lncRNA)在肿瘤细胞增殖、凋亡和转移等细胞过程的调控中发挥着关键作用。LncRNA CRNDE(结直肠癌差异表达)位于人类16号染色体,已发现在包括结直肠癌(CRC)在内的多种癌症中过表达。在本文中,我们报告lncRNA CRNDE在CRC组织中显著上调,且lncRNA CRNDE的过表达与晚期病理阶段和更大的肿瘤大小呈正相关。此外,CRNDE的敲低在体外和体内均显著抑制了CRC细胞的增殖并导致其凋亡。此外,RNA免疫沉淀和染色质免疫沉淀分析表明,lncRNA CRNDE可通过与EZH2(多梳抑制复合物2(PRC2)的关键成分)结合,在表观遗传上抑制双特异性磷酸酶5(DUSP5)和CDKN1A的表达,从而促进CRC的发展。总之,我们的数据表明lncRNA CRNDE促进了CRC的进展,是CRC干预的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9105/5596537/319de151292a/cddis2017328f1.jpg

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