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长链非编码RNA CCAT2激活RAB14并在结直肠癌中作为癌基因发挥作用。

Long Non-Coding RNA CCAT2 Activates RAB14 and Acts as an Oncogene in Colorectal Cancer.

作者信息

Wang Dalu, Li Zhilong, Yin Hongzhuan

机构信息

Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Oncol. 2021 Nov 19;11:751903. doi: 10.3389/fonc.2021.751903. eCollection 2021.

DOI:10.3389/fonc.2021.751903
PMID:34868956
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8639683/
Abstract

Here, we investigated the clinicopathological and prognostic potential of the long noncoding RNA Colon Cancer-Associated Transcript 2 (CCAT2) in human colorectal cancer (CRC). We used qPCR to quantify CCAT2 levels in 44 pairs of CRC tissues and adjacent nontumor and healthy colon mucosa tissues, and in several CRC cell lines (SW620, SW480, HT-29, LOVO, HCT116 and DLD-1) and normal human colorectal epithelial cells (HFC). We assessed the effects of CCAT2 overexpression or knockdown on the proliferation, migration and invasion by SW620 and LOVO cells using CCK-8, transwell, and wound-healing assays, respectively. We also investigated the potential interaction between CCAT2 and TAF15 through RNA pull down and rescue experiments. Lastly, we evaluated the expression of the cell cycle progression markers and GSK3β signaling pathway proteins using Western blotting. Our results showed that CCAT2 was upregulated in CRC tissues and cell lines as com-pared to controls. Ectopic expression of CCAT2 promoted CRC cell proliferation, migration and invasion, likely through direct interaction with TAF15, transcriptional activation of RAB14, and activation of the AKT/GSK3β signaling pathway. , CCAT2 promoted CRC cell growth and metastasis in nude mice. Taken together, these results highlight the actions of CCAT2 as a CRC oncogene.

摘要

在此,我们研究了长链非编码RNA结肠癌相关转录本2(CCAT2)在人类结直肠癌(CRC)中的临床病理特征及预后潜力。我们使用qPCR对44对CRC组织、相邻的非肿瘤及健康结肠黏膜组织,以及几种CRC细胞系(SW620、SW480、HT - 29、LOVO、HCT116和DLD - 1)和正常人结肠上皮细胞(HFC)中的CCAT2水平进行定量。我们分别使用CCK - 8、Transwell和伤口愈合试验评估了CCAT2过表达或敲低对SW620和LOVO细胞增殖、迁移和侵袭的影响。我们还通过RNA下拉和拯救实验研究了CCAT2与TAF15之间的潜在相互作用。最后,我们使用蛋白质印迹法评估细胞周期进展标志物和GSK3β信号通路蛋白的表达。我们的结果表明,与对照组相比,CCAT2在CRC组织和细胞系中上调。CCAT2的异位表达促进了CRC细胞的增殖、迁移和侵袭,可能是通过与TAF15直接相互作用、RAB14的转录激活以及AKT/GSK3β信号通路的激活。此外,CCAT2促进了裸鼠体内CRC细胞的生长和转移。综上所述,这些结果突出了CCAT2作为CRC癌基因的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa0/8639683/5c8c92048440/fonc-11-751903-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3aa0/8639683/5c8c92048440/fonc-11-751903-g008.jpg
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