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HIF-1α 诱导的长链非编码 RNA LINC00511 通过正反馈环加速结直肠癌增殖。

HIF-1α induced lncRNA LINC00511 accelerates the colorectal cancer proliferation through positive feedback loop.

机构信息

Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Department of Gastroenterology, Zhengzhou Central Hospital affiliated to Zhengzhou University, Zhengzhou, Henan, China.

出版信息

Biomed Pharmacother. 2020 May;125:110014. doi: 10.1016/j.biopha.2020.110014. Epub 2020 Feb 25.

Abstract

Long noncoding RNAs lncRNAs play an essential role in the epigenetic regulation of colorectal cancer CRC. However, the biological function of lncRNA Long Intergenic Noncoding RNA 00511 LINC00511 in the CRC is unclear. Here, present research found that LINC00511 was significantly up-regulated in the CRC tissue samples and cell lines. Consistently, LINC00011 overexpression was correlated with larger tumor size and advanced tumor stage. Functionally, LINC00511 promoted the proliferation and reduced the apoptosis of CRC cells in vitro, and LINC00511 knockdown repressed tumor growth in vivo. Mechanistically, hypoxia-inducible factor 1α (HIF-1α) bound the promoter region of LINC00511 to active tits transcription. Moreover, LINC00511 functioned as the miR-153-5p sponge in the cytoplasmic portion, and miR-153-5p also targeted the 3'-UTR of HIF-1α. In conclusion, this study identifies the roles of LINC00511 in CRC progression and uncovers the positive feedback loop of HIF-1α/LINC00511/miR-153-5p in CRC, providing a potential therapeutic target.

摘要

长非编码 RNA(lncRNAs)在结直肠癌(CRC)的表观遗传调控中发挥着重要作用。然而,lncRNA 长基因间非编码 RNA 00511(LINC00511)在 CRC 中的生物学功能尚不清楚。本研究发现,LINC00511 在 CRC 组织样本和细胞系中显著上调。一致地,LINC00511 的过表达与更大的肿瘤大小和更晚期的肿瘤分期相关。功能上,LINC00511 促进 CRC 细胞的增殖并减少其凋亡,而 LINC00511 的敲低则抑制体内肿瘤生长。机制上,缺氧诱导因子 1α(HIF-1α)结合 LINC00511 的启动子区域来激活其转录。此外,LINC00511 在细胞质部分作为 miR-153-5p 的海绵,而 miR-153-5p 也靶向 HIF-1α 的 3'-UTR。总之,本研究确定了 LINC00511 在 CRC 进展中的作用,并揭示了 HIF-1α/LINC00511/miR-153-5p 在 CRC 中的正反馈环,为潜在的治疗靶点提供了依据。

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