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长链基因间非编码RNA 00152通过与EZH2结合并抑制胃癌中的p15和p21来促进肿瘤细胞周期进程。

Long intergenic non-coding RNA 00152 promotes tumor cell cycle progression by binding to EZH2 and repressing p15 and p21 in gastric cancer.

作者信息

Chen Wen-ming, Huang Ming-de, Sun Dao-ping, Kong Rong, Xu Tong-peng, Xia Rui, Zhang Er-bao, Shu Yong-qian

机构信息

Department of Oncology, Jining NO.1 People's Hospital, Jining City, Shandong Province 272011, China.

Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Jiangsu Province 223300, China.

出版信息

Oncotarget. 2016 Mar 1;7(9):9773-87. doi: 10.18632/oncotarget.6949.

Abstract

Long noncoding RNAs (lncRNAs) play important regulatory roles in several human cancers. Integrated analysis revealed that expression of long intergenic non-coding RNA 152 (LINC00152) was significantly upregulated in gastric cancer (GC). Further analysis in a cohort of 97 GC patients revealed that LINC00152 expression was positively correlated with tumor invasion depth, lymph node metastasis, higher TNM stage, and poor survival. Gene set enrichment analysis revealed that cell proliferation and cell cycle progression were increased in patients with high LINC00152 expression. In both GC cell lines and xenograft systems, LINC00152 overexpression facilitated GC cell proliferation by accelerating the cell cycle, whereas LINC00152 knockdown had the opposite effect. Moreover, by binding to enhancer of zeste homolog 2 (EZH2), LINC00152 promotes GC tumor cell cycle progression by silencing the expression of p15 and p21. These findings suggest that LINC00152 may play contribute to the progression of GC and may be an effective therapeutic target.

摘要

长链非编码RNA(lncRNAs)在多种人类癌症中发挥着重要的调控作用。综合分析显示,长链基因间非编码RNA152(LINC00152)在胃癌(GC)中的表达显著上调。对97例GC患者的进一步分析表明,LINC00152的表达与肿瘤浸润深度、淋巴结转移、较高的TNM分期及较差的生存率呈正相关。基因集富集分析显示,LINC00152高表达的患者细胞增殖和细胞周期进程加快。在GC细胞系和异种移植系统中,LINC00152过表达通过加速细胞周期促进GC细胞增殖,而LINC00152敲低则产生相反的效果。此外,LINC00152通过与zeste同源物2(EZH2)增强子结合,使p15和p21的表达沉默,从而促进GC肿瘤细胞周期进程。这些发现表明,LINC00152可能参与了GC的进展,可能是一个有效的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f71/4891083/fbd457a232c1/oncotarget-07-09773-g001.jpg

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