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Long non-coding RNA CCAT1 promotes colorectal cancer progression by regulating miR-181a-5p expression

机译:长非编码RNA CCAT1通过调节miR-181a-5p表达促进结直肠癌的进展

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摘要

The vital roles of long noncoding RNAs (lncRNAs) have been implicated in growing number of studies in tumor development. LncRNA CCAT1 has been recognized as associated with tumor development, yet its relation with colorectal cancer (CRC) remains elusive. Our study aimed at elucidating the function and mechanisms of long non-coding RNA CCAT1 in CRC. From a lncRNA profile dataset of 38 pairs of matched tumor-control colon tissues from colorectal patients housed in The Cancer Genome Atlas (TCGA), we detected 10 upregulated and 10 down-regulated lncRNAs in CRC. Fifty cases of CRC patients were enrolled to analyze the correlation between the expression of CCAT1 and clinical pathology. The inverse correlation of expression and target relationship between CCAT1 and miR-181a-5p were verified using qRT-PCR and dual-luciferase reporter gene assay. Cell viability, colony formation ability, aggression and apoptosis were determined by MTT assay, colony formation assay, Transwell and wound healing assays and flow cytometry analysis. Furthermore, Xenograft model was used to show that knockdown of CCAT1 inhibits tumor growth in vivo. The expression of lncRNA CCAT1 was significantly upregulated in CRC tissues. The CCAT1 expression was positively associated with cancer stage (American Joint Committee on Cancer stage, <0.05). CCAT1 promoted cell proliferation, growth and mobility by targeting miR-181a-5p and the silence of CCAT1 increased the cell apoptosis. Same effect was observed in an in vivo xenograft model, which the tumor size and pro-tumor proteins were significantly diminished by knocking down of CCAT1.
机译:长的非编码RNA(lncRNA)的至关重要的作用已经牵涉到越来越多的肿瘤发展研究中。 LncRNA CCAT1已被认为与肿瘤的发展有关,但其与结直肠癌(CRC)的关系仍然难以捉摸。我们的研究旨在阐明CRC中长非编码RNA CCAT1的功能和机制。从癌症基因组图谱(TCGA)中的大肠患者的38对匹配的肿瘤对照结肠组织的lncRNA配置文件数据集中,我们在CRC中检测到10个上调和10个下调的lncRNA。招募了50例CRC患者,以分析CCAT1表达与临床病理之间的相关性。使用qRT-PCR和双荧光素酶报告基因检测验证了CCAT1和miR-181a-5p之间的表达和靶标关系呈负相关。通过MTT测定,集落形成测定,Transwell和伤口愈合测定以及流式细胞术分析确定细胞活力,集落形成能力,侵袭和凋亡。此外,异种移植模型被用来显示CCAT1的抑制在体内抑制肿瘤的生长。 CRC组织中lncRNA CCAT1的表达明显上调。 CCAT1表达与癌症分期呈正相关(美国癌症分期联合委员会,<0.05)。 CCAT1通过靶向miR-181a-5p促进细胞增殖,生长和迁移,而CCAT1的沉默增加了细胞凋亡。在体内异种移植模型中观察到了相同的效果,通过敲低CCAT1,肿瘤的大小和促肿瘤蛋白显着降低。

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