Long Non-Coding RNA TTN-AS1 Promotes the Proliferation and Invasion of Colorectal Cancer Cells by Activating miR-497-Mediated PI3K/Akt/mTOR Signaling
Long Non-Coding RNA TTN-AS1 Promotes the Proliferation and Invasion of Colorectal Cancer Cells by Activating miR-497-Mediated PI3K/Akt/mTOR Signaling
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DOI：
10.2147/ott.s229104
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Lv, Yanfeng
中科院分区：
文献类型：
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作者：
Cui, Zhenhua;Han, Bingbing;Lv, Yanfeng
前言：长链非编码RNA（lncRNA）由于其在许多癌症中的调节功能而受到越来越多的关注。本研究旨在探讨lncRNATTN-AS 1在结直肠癌（CRC）中的作用及其机制。采用MTT法、transwell法、western blot法和裸鼠移植瘤法检测TTN-AS 1对大肠癌细胞增殖、迁移、侵袭、EMT和体内成瘤的影响。结果：TTN-AS 1在结直肠癌组织和细胞系中的表达水平均显著高于正常对照组。TTN-AS 1高表达预示着结直肠癌患者预后不良，并与侵袭性临床病理特征相关。在功能上，获得和丧失功能的研究表明，TTN-AS 1敲低抑制体外CRC细胞的增殖，迁移，侵袭和上皮间质转化，而TTN-AS 1过表达显示出完全相反的效果。结论：TTN-AS 1可直接与miR-497相互作用，与miR-497模拟物共转染可阻断PI 3 K/Akt/mTOR信号通路的激活，逆转TTN-AS 1过表达对结直肠癌细胞的影响。
Introduction: Long non-coding RNAs (lncRNAs) have obtained increasing attention due to their regulatory functions in many cancers. This work aimed to investigate the functional roles of lncRNATTN-AS1 in colorectal cancer (CRC) and to explore the underlying mechanisms.Methods: The expression profiles of TTN-AS1 and miR-497 in CRC tissues and cell lines were determined by RT-qPCR analysis. MTT assay, transwell assay, western blot analysis, and xenograft tumors in nude mice were employed to analyze the effects of TTN-AS1 on the proliferation, migration, invasion, EMT, and in vivo tumorigenesis of CRC cells. Bioinformatics analysis and dual-luciferase reporter assay determined the direct binding relation between TTN-AS1 and miR-497 in CRC.Results: We observed a significant increase of TTN-AS1 expression level in CRC tissues and cell lines compared with normal counterparts. High expression of TTN-AS1 predicted a poor prognosis and was correlated with aggressive clinicopathological characteristics in CRC patients. Functionally, gain- and loss-of-function studies indicated that TTN-AS1 knockdown suppressed the proliferation, migration, invasion and epithelial-mesenchymal transition of CRC cells in vitro, whereas TTN-AS1 overexpression showed the complete opposite effects. Mechanistically, we found that TTN-AS1 could directly interact with miR-497, and co-transfection with miR-497 mimics blocked the activation of PI3K/Akt/mTOR signaling, and reversed the effects of TTN-AS1 overexpression in CRC cells.Conclusion: To conclude, our findings provide novel insight into CRC tumorigenesis and indicate that TTN-AS1 may serve as a potential therapeutic target for CRC treatment.