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NUDT21 alters glioma migration through differential alternative polyadenylation of LAMC1

Venkata Soumith Jonnakuti1,2,3,4, Ping Ji5, Yipeng Gao3

  • 1Department of Pediatrics, Baylor College of Medicine, Houston, TX, 77030, USA.

Journal of Neuro-Oncology
|June 30, 2023
PubMed
Abstract

Insights

NUDT21 regulates glioma cell behavior by controlling LAMC1 alternative polyadenylation (APA). Shortening of LAMC1's 3' untranslated region (UTR) enhances its expression, promoting glioma cell migration and predicting poor prognosis.

Area of Science:

  • * Molecular biology
  • * Cancer research
  • * Genomics

Background:

  • * Glioma progression involves complex interactions between tumor cells and their microenvironment.
  • * Posttranscriptional regulatory mechanisms, particularly alternative polyadenylation (APA), are crucial but poorly understood in glioma.
  • * Understanding these mechanisms can reveal novel therapeutic targets for glioma.

Purpose of the Study:

  • * To investigate the role of NUDT21 in regulating alternative polyadenylation (APA) dynamics in glioma cells.
  • * To identify NUDT21-regulated APA targets and their impact on glioma tumorigenicity.
  • * To elucidate the functional consequences of NUDT21-mediated APA on glioma cell behavior and patient prognosis.

Main Methods:

  • * PAC-seq (poly(A) tail sequencing) was employed to analyze APA dynamics.
  • * PolyAMiner bioinformatic pipeline was utilized for data analysis.
  • * Quantitative reverse transcription PCR (qRT-PCR) and functional assays were performed to validate findings.

Main Results:

  • * LAMC1 was identified as a key APA target regulated by NUDT21 in glioma.
  • * NUDT21 knockdown led to 3' untranslated region (UTR) shortening of LAMC1, increasing its translation and protein levels.
  • * Shortened LAMC1 3' UTR relieved miR-124/506 repression, promoted glioma cell migration, and correlated with poor prognosis in low-grade glioma patients.

Conclusions:

  • * NUDT21 is a critical APA factor influencing the glioma microenvironment.
  • * NUDT21-mediated LAMC1 3' UTR shortening contributes to increased LAMC1 expression and enhanced glioma cell migration.
  • * These findings highlight NUDT21 and LAMC1 as potential therapeutic targets and prognostic biomarkers in glioma.
Keywords:
Alterative polyadenylationLAMC1NUDT21PolyA-miner

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