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lncRNA-BCAT1与β-连环蛋白通路的相互调控揭示lncRNA-BCAT1长链非编码RNA在结直肠癌中作为肿瘤抑制因子发挥作用。

Reciprocal control of lncRNA-BCAT1 and β-catenin pathway reveals lncRNA-BCAT1 long non-coding RNA acts as a tumor suppressor in colorectal cancer.

作者信息

Xie Fei, Xiang Xudong, Huang Qionglin, Ran Pengzhan, Yuan Yuncang, Li Qian, Qi Guoxiang, Guo Xiaopeng, Xiao Chunjie, Zheng Shangyong

机构信息

School of Medicine, Yunnan University, Kunming, Yunnan 650091, P.R. China.

Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, P.R. China.

出版信息

Oncotarget. 2017 Apr 4;8(14):23628-23637. doi: 10.18632/oncotarget.15466.

DOI:10.18632/oncotarget.15466
PMID:28416735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5410332/
Abstract

β-catenin plays a major role in tumor development and progression. The present study found that β-catenin was upregulated in 30 samples of colorectal cancer (CRC) tissue as compared to adjacent non-tumor tissues. Analysis of long non-coding RNA (lncRNA) expression profiles using the GSE18560 and GSE44097 datasets, which were generated via the Affymetrix plus 2.0 microarray platform and downloaded from the GEO database, revealed 20 differentially expressed lncRNAs following β-catenin knockdown. We focused on AK091631, a novel lncRNA, which we named lncRNA-β-catenin associated transcript 1 (LncRNA-BCAT1). lncRNA-BCAT1 expression was decreased in CRC tissues, and was negatively associated with β-catenin in both CRC tissues and cell lines. lncRNA-BCAT1 overexpression suppressed CRC cell growth and invasion by downregulating cyclin D1, c-Myc, and MMP-2. These results suggest that lncRNA-BCAT1 overexpression inhibits CRC cell growth and invasion via Wnt/β-catenin pathway blockade, and that lncRNA-BCAT1 is repressed by Wnt/β-catenin signaling. This evidence suggests that lncRNA-BCAT1 is a tumor suppressor and that lncRNA-BCAT1 may be an effective prognostic biomarker in CRC.

摘要

β-连环蛋白在肿瘤的发生和发展中起主要作用。本研究发现，与相邻的非肿瘤组织相比，β-连环蛋白在30份结直肠癌（CRC）组织样本中表达上调。使用通过Affymetrix plus 2.0微阵列平台生成并从GEO数据库下载的GSE18560和GSE44097数据集分析长链非编码RNA（lncRNA）表达谱，结果显示在β-连环蛋白敲低后有20种差异表达的lncRNA。我们聚焦于一种新型lncRNA AK091631，将其命名为lncRNA-β-连环蛋白相关转录本1（LncRNA-BCAT1）。LncRNA-BCAT1在CRC组织中的表达降低，并且在CRC组织和细胞系中均与β-连环蛋白呈负相关。LncRNA-BCAT1的过表达通过下调细胞周期蛋白D1、c-Myc和MMP-2来抑制CRC细胞的生长和侵袭。这些结果表明，LncRNA-BCAT1的过表达通过Wnt/β-连环蛋白信号通路阻滞抑制CRC细胞的生长和侵袭，并且LncRNA-BCAT1受到Wnt/β-连环蛋白信号的抑制。这一证据表明LncRNA-BCAT1是一种肿瘤抑制因子，并且LncRNA-BCAT1可能是CRC中一种有效的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/949ce76af878/oncotarget-08-23628-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/cbbebf3bdbdd/oncotarget-08-23628-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/4f64218b219c/oncotarget-08-23628-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/fc8c4b4465e0/oncotarget-08-23628-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/650ccb9188cf/oncotarget-08-23628-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/af03b66e591d/oncotarget-08-23628-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/949ce76af878/oncotarget-08-23628-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/cbbebf3bdbdd/oncotarget-08-23628-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/4f64218b219c/oncotarget-08-23628-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/fc8c4b4465e0/oncotarget-08-23628-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/650ccb9188cf/oncotarget-08-23628-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/af03b66e591d/oncotarget-08-23628-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/932a/5410332/949ce76af878/oncotarget-08-23628-g006.jpg

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