Suppr超能文献

人类癌症中的 RNA 结合蛋白 HuR:是敌是友?

The RNA-binding protein HuR in human cancer: A friend or foe?

机构信息

Higuchi Biosciences Center, The University of Kansas, Lawrence, KS, USA; The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA.

The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS, USA; Department of Molecular Biosciences, The University of Kansas, Lawrence, KS, USA; Department of Radiation Oncology, The University of Kansas Medical Center, Kansas City, KS, USA.

出版信息

Adv Drug Deliv Rev. 2022 May;184:114179. doi: 10.1016/j.addr.2022.114179. Epub 2022 Mar 3.

Abstract

The RNA-binding proteins (RBPs) are critical trans factors that associate with specific cis elements present in mRNAs whose stability and translation are subject to regulation. The RBP Hu antigen R (HuR) is overexpressed in a wide variety of human cancers and serves as a prognostic factor of poor clinical outcome. HuR promotes tumorigenesis by interacting with a subset of oncogenic mRNAs implicated in different cancer hallmarks, and resistance to therapy. Reduction of HuR levels in cancer cells leads to tumor regression in mouse xenograft models. These findings prompt a working model whereby cancer cells use HuR, a master switch of multiple oncogenic mRNAs, to drive drug resistance and promote cell survival and metastasis, thus rendering the tumor cells with high cytoplasmic HuR more progressive and resistant to therapy. This review summarizes the roles of HuR in cancer and other diseases, therapeutic potential of HuR inhibition, and the current status of drug discovery on HuR.

摘要

RNA 结合蛋白 (RBPs) 是关键的转录因子,它们与存在于 mRNA 中的特定顺式元件结合,mRNA 的稳定性和翻译受到调节。RNA 结合蛋白 Hu 抗原 R (HuR) 在多种人类癌症中过度表达,是预后不良的临床结局的预后因素。HuR 通过与一组参与不同癌症特征和治疗耐药性的致癌 mRNA 相互作用促进肿瘤发生。降低癌细胞中的 HuR 水平可导致小鼠异种移植模型中的肿瘤消退。这些发现提示了一种工作模型,即癌细胞利用 HuR(多种致癌 mRNA 的主开关)来驱动耐药性并促进细胞存活和转移,从而使具有高细胞质 HuR 的肿瘤细胞更具侵袭性并对治疗产生耐药性。这篇综述总结了 HuR 在癌症和其他疾病中的作用、HuR 抑制的治疗潜力以及 HuR 药物发现的现状。

相似文献

1
The RNA-binding protein HuR in human cancer: A friend or foe?
Adv Drug Deliv Rev. 2022 May;184:114179. doi: 10.1016/j.addr.2022.114179. Epub 2022 Mar 3.
2
Identification of tumorigenesis-related mRNAs associated with RNA-binding protein HuR in thyroid cancer cells.
Oncotarget. 2016 Sep 27;7(39):63388-63407. doi: 10.18632/oncotarget.11255.
3
An RNA-Binding Protein, Hu-antigen R, in Pancreatic Cancer Epithelial to Mesenchymal Transition, Metastasis, and Cancer Stem Cells.
Mol Cancer Ther. 2020 Nov;19(11):2267-2277. doi: 10.1158/1535-7163.MCT-19-0822. Epub 2020 Sep 2.
4
Identification and validation of novel small molecule disruptors of HuR-mRNA interaction.
ACS Chem Biol. 2015 Jun 19;10(6):1476-84. doi: 10.1021/cb500851u. Epub 2015 Mar 17.
5
HuR as a molecular target for cancer therapeutics and immune-related disorders.
Adv Drug Deliv Rev. 2022 Sep;188:114442. doi: 10.1016/j.addr.2022.114442. Epub 2022 Jul 8.
6
Understanding and targeting the disease-related RNA binding protein human antigen R (HuR).
Wiley Interdiscip Rev RNA. 2020 May;11(3):e1581. doi: 10.1002/wrna.1581. Epub 2020 Jan 23.
7
Targeting the RNA-Binding Protein HuR in Cancer.
Cancer Res. 2023 Nov 1;83(21):3507-3516. doi: 10.1158/0008-5472.CAN-23-0972.

引用本文的文献

1
Integrated pan-cancer analysis of RNA binding protein HuR investigates its biomarker potential in prognosis, immunotherapy, and drug sensitivity.
PLoS Comput Biol. 2025 Aug 25;21(8):e1013374. doi: 10.1371/journal.pcbi.1013374. eCollection 2025 Aug.
2
Multifaceted Human Antigen R (HuR): A Key Player in Liver Metabolism and MASLD.
Livers. 2025 Sep;5(3). doi: 10.3390/livers5030033. Epub 2025 Jul 21.
3
Deciphering the multifaceted role of circular RNA in aging: from molecular mechanisms to therapeutic potentials.
Noncoding RNA Res. 2025 May 30;14:129-144. doi: 10.1016/j.ncrna.2025.05.015. eCollection 2025 Oct.
4
The epigenetic regulatory network of long noncoding RNAs in hepatocellular carcinoma.
Genes Dis. 2025 Jan 20;12(5):101534. doi: 10.1016/j.gendis.2025.101534. eCollection 2025 Sep.
5
Circular RNA TFRC/SCD1 mRNA interaction regulates ferroptosis and metastasis in gastric cancer.
Cell Death Dis. 2025 Jun 5;16(1):436. doi: 10.1038/s41419-025-07759-x.
6
Deciphering the role of : Insights from pan-cancer multiomics analyses with emphasis on nasopharyngeal carcinoma.
J Transl Int Med. 2025 May 8;13(2):138-155. doi: 10.1515/jtim-2025-0009. eCollection 2025 Apr.

本文引用的文献

1
Hallmarks of Cancer: New Dimensions.
Cancer Discov. 2022 Jan;12(1):31-46. doi: 10.1158/2159-8290.CD-21-1059.
2
The RNA binding protein human antigen R is a gatekeeper of liver homeostasis.
Hepatology. 2022 Apr;75(4):881-897. doi: 10.1002/hep.32153. Epub 2021 Dec 5.
4
The RNA-binding protein HuR is a novel target of Pirh2 E3 ubiquitin ligase.
Cell Death Dis. 2021 Jun 5;12(6):581. doi: 10.1038/s41419-021-03871-w.
5
Adipocyte-specific deletion of HuR induces spontaneous cardiac hypertrophy and fibrosis.
Am J Physiol Heart Circ Physiol. 2021 Jul 1;321(1):H228-H241. doi: 10.1152/ajpheart.00957.2020. Epub 2021 May 21.
6
HuR up-regulates cell surface PD-L1 via stabilizing CMTM6 transcript in cancer.
Oncogene. 2021 Mar;40(12):2230-2242. doi: 10.1038/s41388-021-01689-6. Epub 2021 Mar 1.
7
Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors.
Cancer Res. 2021 Apr 15;81(8):2220-2233. doi: 10.1158/0008-5472.CAN-20-2858. Epub 2021 Feb 18.
8
An RNA-Binding Protein, Hu-antigen R, in Pancreatic Cancer Epithelial to Mesenchymal Transition, Metastasis, and Cancer Stem Cells.
Mol Cancer Ther. 2020 Nov;19(11):2267-2277. doi: 10.1158/1535-7163.MCT-19-0822. Epub 2020 Sep 2.
9
Poly(ADP-ribosyl)ation enhances HuR oligomerization and contributes to pro-inflammatory gene mRNA stabilization.
Cell Mol Life Sci. 2021 Feb;78(4):1817-1835. doi: 10.1007/s00018-020-03618-4. Epub 2020 Aug 13.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验