ArticleJournal of neuro-oncology2023
NUDT21 alters glioma migration through differential alternative polyadenylation of LAMC1.
Article in Journal of neuro-oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Circular RNA circLAMC1 Promotes Liver Regeneration by Regulating the miR-138-5p/Gnai2 Axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Abnormal levels of miRNA in pancreatic cancer are linked to tumor progression by regulating the translation of tumor-associated mRNA.Annals of medicine · 2025Review
- Unveiling cell-type-specific microRNA networks through alternative polyadenylation in glioblastoma.BMC biology · 2025Article
- WGCNA reveals a biomarker for cancer-associated fibroblasts to predict prognosis in cervical cancer.Journal of the Chinese Medical Association : JCMA · 2024Article
- Glioma actively orchestrate a self-advantageous extracellular matrix to promote recurrence and progression.BMC cancer · 2024Review
- Machine learning to establish three sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with gastric cancer.BMC genomics · 2024Article
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
purposeGliomas and their surrounding microenvironment constantly interact to promote tumorigenicity, yet the underlying posttranscriptional regulatory mechanisms that govern this interplay are poorly understood.
methodsUtilizing our established PAC-seq approach and PolyAMiner bioinformatic analysis pipeline, we deciphered the NUDT21-mediated differential APA dynamics in glioma cells.
resultsWe identified LAMC1 as a critical NUDT21 alternative polyadenylation (APA) target, common in several core glioma-driving signaling pathways. qRT-PCR analysis confirmed that NUDT21-knockdown in glioma cells results in the preferred usage of the proximal polyA signal (PAS) of LAMC1. Functional studies revealed that NUDT21-knockdown-induced 3'UTR shortening of LAMC1 is sufficient to cause translational gain, as LAMC1 protein is upregulated in these cells compared to their respective controls. We demonstrate that 3'UTR shortening of LAMC1 after NUDT21 knockdown removes binding sites for miR-124/506, thereby relieving potent miRNA-based repression of LAMC1 expression. Remarkably, we report that the knockdown of NUDT21 significantly promoted glioma cell migration and that co-depletion of LAMC1 with NUDT21 abolished this effect. Lastly, we observed that LAMC1 3'UTR shortening predicts poor prognosis of low-grade glioma patients from The Cancer Genome Atlas.
conclusionThis study identifies NUDT21 as a core alternative polyadenylation factor that regulates the tumor microenvironment through differential APA and loss of miR-124/506 inhibition of LAMC1. Knockdown of NUDT21 in GBM cells mediates 3'UTR shortening of LAMC1, contributing to an increase in LAMC1, increased glioma cell migration/invasion, and a poor prognosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.