Complex HuR function in pancreatic cancer cells

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with dismal patient outcomes. The underlying core genetic drivers of disease have been identified in human tumor specimens and described in genetically engineered mouse models. These genetic drivers of PDAC include KRAS signaling, TP53 mutations, and genetic loss of the SMAD4 tumor suppressor protein. Beyond the known mutational landscape of PDAC genomes, alternative disrupted targets that extend beyond conventional genetic mutations have been elusive and understudied in the context of PDAC cell therapeutic resistance and survival. This last point is important because PDAC tumors have a unique and complex tumor microenvironment that includes hypoxic and nutrient-deprived niches that could select for cell populations that garner therapeutic resistance, explaining tumor heterogeneity in regards to response to different therapies. We and others have embarked in a line of investigation focused on the key molecular mechanism of posttranscriptional gene regulation that is altered in PDAC cells and supports this pro-survival phenotype intrinsic to PDAC cells. Specifically, the key regulator of this mechanism is a RNA-binding protein, HuR (ELAVL1), first described in cancer nearly two decades ago. Herein, we will provide a brief overview of the work demonstrating the importance of this RNA-binding protein in PDAC biology and then provide insight into ongoing work developing therapeutic strategies aimed at targeting this molecule in PDAC cells.

RNA-Binding Protein HuR Regulates Both Mutant and Wild-Type IDH1 in IDH1-Mutated Cancer

“…Previous studies showed that HuR promotes proliferation in cancer cells (20,38), including wild-type gliomas (39,40). Here, we investigated the effect of HuR expression on cell proliferation in cancer cells that harbor a natural heterozygous IDH1 mutation.…”

Analysis of eEF1Bγ interactome in the nuclear fraction of A549 human lung adenocarcinoma cells

“…There are a number of reports, which link pro-tumor activity of HuR/ELAVL1 with cancer of different localizations [64][65][66][67][68]. Surprisingly, HuR/ELAVL1 binding to different long non-coding RNAs induces opposite effect on the proliferation of different tumor cells [69,70].…”

Construction of an RNA Binding Protein-based Model for Prognosis Prediction of Colorectal Cancer

“…HuR, a member of ELA V family of RBPs ,High HuR protein expression is found in both the nucleus and cytoplasm of human colorectal cancer [14]. HuR protein can recognize and combined messenger RNA of target genes, thus stable target genes to inhibit the degradation of messenger RNA, participate in the post-transcriptional regulation of target genes, and regulate a variety of physiological and biochemical processes such as tumor cell growth, proliferation, differentiation, signal transduction, transcription and translation, angiogenesis, protein transport, cell apoptosis and its metabolism [31]. The insulin-like growth factor-2 mRNA binding proteins (IGF2BPs or IMPs) belong to a conserved subfamily of RBPs.…”