Department of Laboratory Medicine, Tongji Hospital of Tongji University School of Medicine, Shanghai, 200065, China.
Department of Pathology, The Sixth People's Hospital of Yancheng, Yancheng 224001, Jiangsu, China.
Aging (Albany NY). 2020 May 7;12(9):8301-8320. doi: 10.18632/aging.103139.
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.
长链非编码 RNA（lncRNAs）的重要作用已在越来越多的肿瘤发生研究中得到证实。lncRNA CCAT1 已被认为与肿瘤发生有关，但它与结直肠癌（CRC）的关系仍不清楚。我们的研究旨在阐明长非编码 RNA CCAT1 在 CRC 中的功能和机制。从 38 对来自结直肠癌患者的配对肿瘤-对照结肠组织的 lncRNA 图谱数据集（位于 The Cancer Genome Atlas（TCGA）中）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 患者来分析 CCAT1 的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 与 miR-181a-5p 的表达反相关和靶关系。通过 MTT 测定、集落形成测定、Transwell 和划痕愈合测定以及流式细胞术分析测定细胞活力、集落形成能力、侵袭和凋亡。此外，还使用异种移植模型表明，CCAT1 的敲低抑制体内肿瘤生长。CRC 组织中 lncRNA CCAT1 的表达明显上调。CCAT1 的表达与癌症分期（美国癌症联合委员会分期，<0.05）呈正相关。CCAT1 通过靶向 miR-181a-5p 促进细胞增殖、生长和迁移，沉默 CCAT1 增加细胞凋亡。在体内异种移植模型中也观察到相同的效果，敲低 CCAT1 显著减小了肿瘤大小和促肿瘤蛋白。
