HuR Protein in Hepatocellular Carcinoma: Implications in Development, Prognosis and Treatment

Abstract

Hu-antigen R (HuR) is a post-transcriptional regulator that belongs to the embryonic lethal abnormal vision Drosophila-like family (ELAV). HuR regulates the stability, translation, subcellular localization, and degradation of several target mRNAs, which are implicated in carcinogenesis and could affect therapeutic options. HuR protein is consistently highly expressed in hepatocellular carcinoma (HCC) compared to the adjacent normal liver tissue and is involved in the post-transcriptional regulation of various genes implicated in liver malignant transformation. Additionally, HuR protein seems to be a putative prognosticator in HCC, predicting worse survival. This review summarizes the recent evidence regarding the role of HuR in primary liver tumors, as presented in clinical studies, in vitro experiments and in vivo animal models. In conclusion, our review supports the consistent role of HuR protein in the development, prognosis, and treatment of HCC. Additional studies are expected to expand current information and exploit its putative employment as a future candidate for more personalized treatment in these tumors.

ADORA2A-AS1 Restricts Hepatocellular Carcinoma Progression via Binding HuR and Repressing FSCN1/AKT Axis

“…These results demonstrated that ADORA2A-AS1 specifically bound to HuR. HuR is reported to bind and stabilize several mRNAs, including FSCN1, VEGFC, MAT2A, MDM2, CCND1, CASP3, USP7, FAS, PDGFA, CTSS, GATA3, and EGFR (41)(42)(43)(44)(45)(46). The RNA-seq data of HCC tissues from TCGA project showed that among all these HuR targets, FSCN1 has the most significant correlation with ADORA2A-AS1 with r value of -0.4627 (Figure 5C and Figure S2).…”

“…Previous reports have shown that high expression of HuR was associated with poor survival in HCC (45). HuR promotes HCC malignant progression via regulating several mRNA targets (45).…”

“…HuR posttranscriptionally regulates expression of target genes via directly binding target mRNAs and further stabilizing target mRNAs (54). Previous reports have shown that high expression of HuR was associated with poor survival in HCC (45). HuR promotes HCC malignant progression via regulating several mRNA targets (45).…”

Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis

“…In MCF-7 cells also, miR-21 was shown to be sequestered by the RNA-binding protein HuR, thereby preventing mRNA decay of PDCD4 , a classical target of miR-21 [ 93 ]. Of note, HuR is strongly upregulated in human HCC, where it correlates with a poor prognosis [ 106 ]. It is now also clear that in specific pathological situations mRNAs targeting by miR-21 is likely a matter of a delicate stochiometric equilibrium depending on the amount of miR-21 available, the amount of mRNA target molecules and their competition to bind miR-21, as well as the titration of free miR-21 by irrelevant targets or pseudogenes [ 107 ].…”

S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent

“…mRNA-binding proteins are involved in the post-transcriptional deregulation of gene expression. Thus, AUF1 increases mRNA decay while HuR selectively binds to AU-rich elements increasing mRNA stability [32,[46][47][48][49]. Interestingly, Mat1A decrease, Mat1A:Mat2A switch, and low SAM levels are associated with CpG hypermethylation and histone H4 deacetylation of Mat1A promoter, and prevalent CpG hypomethylation and histone H4 acetylation of Mat2A promoter.…”