Related Experiment Video

Updated: Sep 6, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

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ALYREF, a novel factor involved in breast carcinogenesis, acts through transcriptional and post-transcriptional

Christiane Klec1,2, Erik Knutsen3,4, Daniela Schwarzenbacher1,2

  • 1Division of Oncology, Department of Internal Medicine, Medical University of Graz, Augenbruggerplatz 15, 8010, Graz, Austria.

Cellular and Molecular Life Sciences : CMLS
|July 1, 2022
PubMed

Insights

High expression of the RNA-binding protein ALYREF (THOC4) correlates with poor breast cancer survival. ALYREF promotes breast cancer by regulating the NEAT1 lncRNA, impacting cell growth and metabolism.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • The RNA-binding protein ALYREF (THOC4) has known roles in transcription and mRNA export.
  • Its specific function and mechanism in breast cancer development remain uncharacterized.

Purpose of the Study:

  • To investigate the role of ALYREF in breast carcinogenesis.
  • To elucidate the molecular mechanisms underlying ALYREF's function in breast cancer.

Main Methods:

  • Analysis of ALYREF expression in breast cancer patient data.
  • In vitro studies on breast cancer cell lines assessing growth, apoptosis, and metabolism.
  • Orthotopic mouse models for in vivo tumorigenesis.
  • Transcriptional profiling, phenocopy, and rescue experiments.
  • Investigation of ALYREF interaction with NEAT1 and CPSF6.

Main Results:

  • High ALYREF expression is a predictor of poor survival in breast cancer patients.
  • ALYREF significantly impacts breast cancer cell proliferation, apoptosis, and mitochondrial metabolism.
  • ALYREF enhances the transcription of the short isoform of the long non-coding RNA NEAT1 by binding its promoter.
  • ALYREF stabilizes CPSF6, promoting short NEAT1 isoform generation, and directly stabilizes short NEAT1.

Conclusions:

  • ALYREF is a novel oncogenic factor in breast cancer.
  • ALYREF exerts its oncogenic effects through the NEAT1 lncRNA, specifically fine-tuning the expression of its short isoform.
  • This study reveals new regulatory mechanisms involving ALYREF and NEAT1 isoforms in breast cancer progression.
Keywords:
ALYREFBreast cancerNEAT1Transcriptional regulationlncRNA

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