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长链非编码 RNA MIR17HG 通过 miR-17-5p 促进结直肠癌的进展。

Long Noncoding RNA MIR17HG Promotes Colorectal Cancer Progression via miR-17-5p.

机构信息

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.

Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, China.

出版信息

Cancer Res. 2019 Oct 1;79(19):4882-4895. doi: 10.1158/0008-5472.CAN-18-3880. Epub 2019 Aug 13.

Abstract

Immune dysregulation plays a vital role in colorectal cancer initiation and progression. Long noncoding RNAs (lncRNA) exhibit multiple functions including regulation of gene expression. Here, we identified an immune-related lncRNA, MIR17HG, whose expression was gradually upregulated in adjacent, adenoma, and colorectal cancer tissue. MIR17HG promoted tumorigenesis and metastasis in colorectal cancer cells both and . Mechanistically, MIR17HG increased the expression of NF-κB/RELA by competitively sponging the microRNA miR-375. In addition, RELA transcriptionally activated MIR17HG in a positive feedback loop by directly binding to its promoter region. Moreover, miR-17-5p, one of the transcribed miRNAs from MIR17HG, reduced the expression of the tumor suppressor B-cell linker (BLNK), resulting in increased migration and invasion of colorectal cancer cells. MIR17HG also upregulated PD-L1, indicating its potential role in immunotherapy. Overall, these findings demonstrate that MIR17HG plays an oncogenic role in colorectal cancer and may serve as a promising therapeutic target. SIGNIFICANCE: These findings provide mechanistic insight into the role of the lncRNA MIR17HG and its miRNA members in regulating colorectal cancer carcinogenesis and progression.

摘要

免疫失调在结直肠癌的发生和发展中起着至关重要的作用。长链非编码 RNA(lncRNA)具有多种功能,包括调节基因表达。在这里,我们鉴定了一个免疫相关的 lncRNA,MIR17HG,其表达在相邻组织、腺瘤和结直肠癌组织中逐渐上调。MIR17HG 在结直肠癌细胞中促进肿瘤发生和转移。机制上,MIR17HG 通过竞争性地吸附 microRNA miR-375 来增加 NF-κB/RELA 的表达。此外,RELA 通过直接结合其启动子区域,在正反馈环中转录激活 MIR17HG。此外,MIR17HG 转录的 miRNA 之一 miR-17-5p 降低了肿瘤抑制因子 B 细胞接头(BLNK)的表达,导致结直肠癌细胞迁移和侵袭增加。MIR17HG 还上调了 PD-L1,表明其在免疫治疗中有潜在作用。总之,这些发现表明 MIR17HG 在结直肠癌中发挥致癌作用,可能成为有前途的治疗靶点。

意义

这些发现为 lncRNA MIR17HG 及其 miRNA 成员在调节结直肠癌发生和进展中的作用提供了机制上的见解。

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