ArticleJournal of experimental & clinical cancer research : CR2022
RNA binding protein HuD promotes autophagy and tumor stress survival by suppressing mTORC1 activity and augmenting ARL6IP1 levels.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- The RNA-Binding Protein ELAVL4/HuD Promotes Stress-Associated Tumor Survival in Neuroendocrine Cancers.International journal of molecular sciences · 2026Review
- Identification and functional validation of a four-gene signature associated with radiotherapy resistance in oral squamous cell carcinoma.Translational oncology · 2026Article
- Melatonin induces autophagy in neuroblastoma by alleviating Pak2‑mediated endoplasmic reticulum stress.Molecular medicine reports · 2026Article
- DDR2-mediated autophagy inhibition contributes to angiotensin II-induced adventitial remodeling.Clinical and translational medicine · 2025Article
- Antibody conjugates in neuroblastoma: a step forward in precision medicine.Frontiers in oncology · 2025Review
- Post-transcriptional dynamics and RNA homeostasis in autophagy and cancer.Cell death and differentiation · 2025Review
- STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma.Molecules and cells · 2024Article
- ZNFX1 promotes AMPK-mediated autophagy against Mycobacterium tuberculosis by stabilizing Prkaa2 mRNA.JCI insight · 2024Article
- Article
- RNA Binding Protein Rbms1 Enables Neuronal Differentiation and Radial Migration during Neocortical Development by Binding and Stabilizing the RNA Message for Efr3a.Molecules and cells · 2022Article
- Dysfunctional Glucose Metabolism in Alzheimer's Disease Onset and Potential Pharmacological Interventions.International journal of molecular sciences · 2022Review
- Correction to: RNA binding protein HuD promotes autophagy and tumor stress survival by suppressing mTORC1 activity and augmenting ARL6IP1 levels.Journal of experimental & clinical cancer research : CR · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuronal-origin HuD (ELAVL4) is an RNA binding protein overexpressed in neuroblastoma (NB) and certain other cancers. The RNA targets of this RNA binding protein in neuroblastoma cells and their role in promoting cancer survival have been unexplored. In the study of modulators of mTORC1 activity under the conditions of optimal cell growth and starvation, the role of HuD and its two substrates were studied.
methodsRNA immunoprecipitation/sequencing (RIP-SEQ) coupled with quantitative real-time PCR were used to identify substrates of HuD in NB cells. Validation of the two RNA targets of HuD was via reverse capture of HuD by synthetic RNA oligoes from cell lysates and binding of RNA to recombinant forms of HuD in the cell and outside of the cell. Further analysis was via RNA transcriptome analysis of HuD silencing in the test cells.
resultsIn response to stress, HuD was found to dampen mTORC1 activity and allow the cell to upregulate its autophagy levels by suppressing mTORC1 activity. Among mRNA substrates regulated cell-wide by HuD, GRB-10 and ARL6IP1 were found to carry out critical functions for survival of the cells under stress. GRB-10 was involved in blocking mTORC1 activity by disrupting Raptor-mTOR kinase interaction. Reduced mTORC1 activity allowed lifting of autophagy levels in the cells required for increased survival. In addition, ARL6IP1, an apoptotic regulator in the ER membrane, was found to promote cell survival by negative regulation of apoptosis. As a therapeutic target, knockdown of HuD in two xenograft models of NB led to a block in tumor growth, confirming its importance for viability of the tumor cells. Cell-wide RNA messages of these two HuD substrates and HuD and mTORC1 marker of activity significantly correlated in NB patient populations and in mouse xenografts.
conclusionsHuD is seen as a novel means of promoting stress survival in this cancer type by downregulating mTORC1 activity and negatively regulating apoptosis.
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