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长链非编码RNA的下调通过发挥其增强子样功能损害表达来抑制胃癌细胞的迁移和侵袭。

Downregulation of Long Non-coding RNA Inhibits Gastric Cancer Cell Migration and Invasion Through Impairing Expression by Exerting Its Enhancer-Like Function.

作者信息

Wu Huazhang, Qiao Fengchang, Zhao Yunli, Wu Shouwei, Hu Minjie, Wu Tao, Huang Fuxin, Chen Wenjing, Sun Dengzhong, Liu Mulin, Zhao Jinsong

机构信息

School of Life Sciences, Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Bengbu, China.

Department of Prenatal Diagnosis, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

出版信息

Front Genet. 2019 Mar 22;10:255. doi: 10.3389/fgene.2019.00255. eCollection 2019.

Abstract

Long non-coding RNAs (lncRNAs) have been shown to play important roles in many human diseases. However, their functions and mechanisms in tumorigenesis and development remain largely unknown. Here, we demonstrated that focally amplified lncRNA in epithelial cancer (FALEC) was upregulated and significantly correlated with lymph node metastasis, TNM stage in gastric cancer (GC). Further experiments revealed that FALEC knockdown significantly inhibited GC cells migration and invasion Mechanistic investigations demonstrated that small interfering RNA-induced silencing of FALEC decreased expression of the nearby gene extracellular matrix protein 1 () in Additionally, and expression were positively correlated, and high levels of ECM1 predicted shorter survival time in GC patients. Our results suggest that the downregulation of significantly inhibited the migration and invasion of GC cells through impairing expression by exerting an enhancer-like function. Our work provides valuable information and a novel promising target for developing new therapeutic strategies in GC.

摘要

长链非编码RNA(lncRNAs)已被证明在许多人类疾病中发挥重要作用。然而,它们在肿瘤发生和发展中的功能及机制仍 largely unknown。在此,我们证明上皮癌中的局灶性扩增lncRNA(FALEC)上调,且与胃癌(GC)的淋巴结转移、TNM分期显著相关。进一步实验表明,FALEC敲低显著抑制GC细胞迁移和侵袭。机制研究表明,小干扰RNA诱导的FALEC沉默降低了附近基因细胞外基质蛋白1()的表达。此外,和表达呈正相关,ECM1高水平预示GC患者生存时间较短。我们的结果表明,通过发挥类似增强子的功能损害表达,显著抑制了GC细胞的迁移和侵袭。我们的工作为开发GC新治疗策略提供了有价值的信息和一个新的有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cce/6448009/80dcf8b724c4/fgene-10-00255-g001.jpg

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