HNRNPA2B1 and HNRNPR stabilize ASCL1 mRNA in neuroblastoma, but whether their regulatory effects depend on m6A modification and whether their function involves ASCL1 remain unknown. This study investigated the m6A-dependent binding of HNRNPA2B1 and HNRNPR to ASCL1 and subsequent regulation, as well as the expression, clinical significance, and function of HNRNPA2B1 and HNRNPR in neuroblastoma. We revealed that METTL14 mediated ASCL1 m6A modification to stabilize ASCL1. HNRNPA2B1 and HNRNPR significantly enriched ASCL1 mRNA by binding to the 5' and 3' untranslated regions, respectively, and METTL14 knockdown reduced this enrichment. Mutations in m6A sites in the untranslated regions of ASCL1 mRNA considerably decreased probe capacity to engage HNRNPA2B1 and HNRNPR. HNRNPR interacts with IGF2BP1, and knocking down either impaired binding to ASCL1 mRNA. HNRNPA2B1 and HNRNPR knockdown suppressed neuroblastoma cell growth and invasion, while ASCL1 overexpression restored these effects. The high HNRNPA2B1 and HNRNPR expression in neuroblastoma correlated with ASCL1 expression. Thus, HNRNPA2B1 and HNRNPR bind and stabilize ASCL1 mRNA in an m6A-dependent manner to promote neuroblastoma progression. This study not only discovered a new mechanism underlying the high ASCL1 expression in neuroblastoma but also identified the HNRNPA2B1/HNRNPR/ASCL1 axis as a promising target for inhibiting neuroblastoma progression.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbadis.2024.167050 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
HNRNPA2B1 and HNRNPR stabilize ASCL1 in an m6A-dependent manner to promote neuroblastoma progression.
Biochim Biophys Acta Mol Basis Dis
March 2024
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410008, China; Institute of Skull Base Surgery and Neurooncology at Hunan Province, Changsha 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address:
HNRNPA2B1 and HNRNPR stabilize ASCL1 mRNA in neuroblastoma, but whether their regulatory effects depend on m6A modification and whether their function involves ASCL1 remain unknown. This study investigated the m6A-dependent binding of HNRNPA2B1 and HNRNPR to ASCL1 and subsequent regulation, as well as the expression, clinical significance, and function of HNRNPA2B1 and HNRNPR in neuroblastoma. We revealed that METTL14 mediated ASCL1 m6A modification to stabilize ASCL1.
View Article and Find Full Text PDFTherapeutic reduction of GGGGCC repeat RNA levels by hnRNPA3 suppresses neurodegeneration in Drosophila models of C9orf72-linked ALS/FTD.
Hum Mol Genet
May 2023
Department of Neurology, Kindai University Faculty of Medicine, Osaka 589-8511, Japan.
The abnormal expansion of GGGGCC hexanucleotide repeats within the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The accumulation of GGGGCC repeat-containing RNAs as RNA foci, and the deposition of dipeptide repeat proteins (DPR) produced from these repeat RNAs by unconventional translation are major pathological hallmarks of C9orf72-linked ALS/FTD (C9-ALS/FTD), and are both thought to play a crucial role in the pathogenesis of these diseases. Because GGGGCC repeat RNA is likely to be the most upstream therapeutic target in the pathogenic cascade of C9-ALS/FTD, lowering the cellular level of GGGGCC repeat RNA is expected to mitigate repeat RNA toxicity, and will therefore be a disease-modifying therapeutic strategy for the treatment of C9-ALS/FTD.
View Article and Find Full Text PDFThe hnRNPK/A1/R/U Complex Regulates Gene Transcription and Translation and is a Favorable Prognostic Biomarker for Human Colorectal Adenocarcinoma.
Front Oncol
July 2022
Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China.
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are emerging as a crucially important protein family in tumors. However, it is unclear which family members are essential for cancer progression, and their diverse expression patterns and prognostic values are rarely reported. In this work, we found that the expression levels of hnRNPs were all upregulated in colon adenocarcinoma (COAD) and rectal adenocarcinoma (READ) tissues.
View Article and Find Full Text PDFShutdown of achaete-scute homolog-1 expression by heterogeneous nuclear ribonucleoprotein (hnRNP)-A2/B1 in hypoxia.
J Biol Chem
September 2014
Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, D-10117 Berlin,. Electronic address:
The basic helix-loop-helix transcription factor hASH1, encoded by the ASCL1 gene, plays an important role in neurogenesis and tumor development. Recent findings indicate that local oxygen tension is a critical determinant for the progression of neuroblastomas. Here we investigated the molecular mechanisms underlying the oxygen-dependent expression of hASH1 in neuroblastoma cells.
View Article and Find Full Text PDFLandscape of the SOX2 protein-protein interactome.
Proteomics
March 2011
Swedish Neuroscience Institute, Swedish Medical Center, Seattle, WA, USA.
SOX2 is a key gene implicated in maintaining the stemness of embryonic and adult stem cells that appears to re-activate in several human cancers including glioblastoma multiforme. Using immunoprecipitation (IP)/MS/MS, we identified 144 proteins that are putative SOX2 interacting proteins. Of note, SOX2 was found to interact with several heterogeneous nuclear ribonucleoprotein family proteins, including HNRNPA2B1, HNRNPA3, HNRNPC, HNRNPK, HNRNPL, HNRNPM, HNRNPR, HNRNPU, as well as other ribonucleoproteins, DNA repair proteins and helicases.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!