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Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors

1
Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain
2
Centro de Investigaciones Científicas Isla de la Cartuja (cicCartuja), Instituto de Investigaciones Químicas (IIQ), Universidad de Sevilla, Consejo Superior de Investigaciones Científicas (CSIC), 41092 Sevilla, Spain
3
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, 28029 Madrid, Spain
*
Author to whom correspondence should be addressed.
Academic Editor: Claudio Tiribelli
Cancers 2022, 14(11), 2666; https://doi.org/10.3390/cancers14112666
Received: 15 April 2022 / Revised: 19 May 2022 / Accepted: 23 May 2022 / Published: 27 May 2022
(This article belongs to the Special Issue Theranostic Advances in Hepatobiliary Tumors)
Hepatobiliary tumors are a group of primary malignancies encompassing the liver, the intra- and extra-hepatic biliary tracts, and the gall bladder. Within the liver, hepatocellular carcinoma (HCC) is the most common type of primary cancer, which is, also, representing the third-most recurrent cause of cancer-associated death and the sixth-most prevalent type of tumor worldwide, nowadays. Although less frequent, cholangiocarcinoma (CCA) is, currently, a fatal cancer with limited therapeutic options. Here, we review the regulatory role of Hu antigen R (HuR), a ubiquitous member of the ELAV/Hu family of RNA-binding proteins (RBPs), in the pathogenesis, progression, and treatment of HCC and CCA. Overall, HuR is proposed as a valuable diagnostic and prognostic marker, as well as a therapeutic target in hepatobiliary cancers. Therefore, novel therapeutic approaches that can selectively modulate HuR function appear to be highly attractive for the clinical management of these types of tumors.
Hu antigen R (HuR) is a 36-kDa ubiquitous member of the ELAV/Hu family of RNA-binding proteins (RBPs), which plays an important role as a post-transcriptional regulator of specific RNAs under physiological and pathological conditions, including cancer. Herein, we review HuR protein structure, function, and its regulation, as well as its implications in the pathogenesis, progression, and treatment of hepatobiliary cancers. In particular, we focus on hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), tumors where the increased cytoplasmic localization of HuR and activity are proposed, as valuable diagnostic and prognostic markers. An overview of the main regulatory axes involving HuR, which are associated with cell proliferation, invasion, metastasis, apoptosis, and autophagy in HCC, is provided. These include the transcriptional, post-transcriptional, and post-translational modulators of HuR function, in addition to HuR target transcripts. Finally, whereas studies addressing the relevance of targeting HuR in CCA are limited, in the past few years, HuR has emerged as a potential therapeutic target in HCC. In fact, the therapeutic efficacy of some pharmacological inhibitors of HuR has been evaluated, in early experimental models of HCC. We, further, discuss the major findings and future perspectives of therapeutic approaches that specifically block HuR interactions, either with post-translational modifiers or cognate transcripts in hepatobiliary cancers. View Full-Text
Keywords: ELAV-like protein 1; RNA-binding protein; hepatocellular carcinoma; cholangiocarcinoma ELAV-like protein 1; RNA-binding protein; hepatocellular carcinoma; cholangiocarcinoma
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MDPI and ACS Style

Lachiondo-Ortega, S.; Delgado, T.C.; Baños-Jaime, B.; Velázquez-Cruz, A.; Díaz-Moreno, I.; Martínez-Chantar, M.L. Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors. Cancers 2022, 14, 2666. https://doi.org/10.3390/cancers14112666

AMA Style

Lachiondo-Ortega S, Delgado TC, Baños-Jaime B, Velázquez-Cruz A, Díaz-Moreno I, Martínez-Chantar ML. Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors. Cancers. 2022; 14(11):2666. https://doi.org/10.3390/cancers14112666

Chicago/Turabian Style

Lachiondo-Ortega, Sofia, Teresa C. Delgado, Blanca Baños-Jaime, Alejandro Velázquez-Cruz, Irene Díaz-Moreno, and María L. Martínez-Chantar. 2022. "Hu Antigen R (HuR) Protein Structure, Function and Regulation in Hepatobiliary Tumors" Cancers 14, no. 11: 2666. https://doi.org/10.3390/cancers14112666

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