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CREB1诱导的长链非编码RNA LEF1-AS1通过miR-489/DIAPH1轴促进结直肠癌进展。

CREB1-induced lncRNA LEF1-AS1 contributes to colorectal cancer progression via the miR-489/DIAPH1 axis.

作者信息

Cheng Yan, Wu Jing, Qin Bin, Zou Bai-Cang, Wang Yong-Hua, Li Yang

机构信息

Department of Digestive Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

出版信息

Biochem Biophys Res Commun. 2020 Jun 4;526(3):678-684. doi: 10.1016/j.bbrc.2020.03.153. Epub 2020 Apr 2.

Abstract

Long non-coding RNAs (lncRNAs) have been identified as new regulatory factors in tumor progression. Lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) was a recently identified lncRNA. This research aimed to investigate the roles and mechanisms of LEF1-AS1 in colorectal cancer (CRC). We firstly showed that LEF1-AS1 expression was upregulated in human CRC tissues and cell lines. LEF1-AS1 upregulation was demonstrated to be induced by CREB1. Clinical study revealed that high LEF1-AS1 expression was positively associated with histological grade, lymph nodes metastasis, and decreased survivals of CRC patients. Functionally, down-regulation of LEF1-AS1 using si-LEF1-AS1 decreased cell growth, migration and invasion, as well as increased apoptosis in CRC cells. Mechanically, LEF1-AS1 functioned as competing endogenous RNA (ceRNA) for miR-489 to positively recover DIAPH1, thus playing an oncogenic role in CRC pathogenesis. Overall, our observations identified a novel CRC-related lncRNA LEF1-AS1 and discovered a critical role for this lncRNA as a ceRNA in CRC pathogenesis, suggesting that it may serve as a novel biomarker for prognosis and act as a therapeutic target for CRC treatment.

摘要

长链非编码RNA(lncRNAs)已被确认为肿瘤进展中的新调控因子。淋巴样增强因子1反义RNA 1(LEF1-AS1)是最近发现的一种lncRNA。本研究旨在探讨LEF1-AS1在结直肠癌(CRC)中的作用及机制。我们首先发现LEF1-AS1在人CRC组织和细胞系中表达上调。LEF1-AS1的上调被证明是由CREB1诱导的。临床研究表明,LEF1-AS1高表达与CRC患者的组织学分级、淋巴结转移及生存率降低呈正相关。在功能上,使用si-LEF1-AS1下调LEF1-AS1可降低CRC细胞的生长、迁移和侵袭,并增加细胞凋亡。机制上,LEF1-AS1作为miR-489的竞争性内源RNA(ceRNA),正向恢复DIAPH1,从而在CRC发病机制中发挥致癌作用。总体而言,我们的观察结果鉴定出一种新的与CRC相关的lncRNA LEF1-AS1,并发现该lncRNA作为ceRNA在CRC发病机制中起关键作用,表明它可能作为一种新的预后生物标志物,并作为CRC治疗的靶点。

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