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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Published on: April 26, 2017

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Alternative polyadenylation in cancer: Molecular mechanisms and clinical application

Ying Zhang1, Zikun Huang2, Weiqing Lu3

  • 1Department of Radiotherapy, Cancer Hospital of Shantou University Medical College, No.7 Raoping Road, Shantou, Guangdong 515041, China; Clinical Research Center, Cancer Hospital of Shantou University Medical College, No.7 Raoping Road, Shantou, Guangdong 515041, China.

Critical Reviews in Oncology/Hematology
|December 19, 2024
PubMed

Insights

Alternative polyadenylation (APA) regulates gene expression by creating mRNA variants, controlled by RNA-binding proteins (RBPs). Dysregulation of APA and RBPs is linked to cancer, suggesting therapeutic potential.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Alternative polyadenylation (APA) is a key posttranscriptional regulatory mechanism generating diverse mRNA isoforms.
  • RNA-binding proteins (RBPs) control APA by binding to specific pre-mRNA sequences or structures.
  • Dysregulation of APA and RBPs is implicated in diseases like cancer, cardiovascular, and nervous system disorders.

Purpose of the Study:

  • To review current knowledge on APA mechanisms and the roles of RBPs.
  • To highlight advancements in high-throughput sequencing and bioinformatics for studying APA.
  • To explore the pathological role of APA dysregulation in oncogenesis and therapeutic potential.

Main Methods:

  • Literature review of APA mechanisms and RBP functions.
  • Evaluation of high-throughput sequencing and bioinformatics tools for genome-wide APA analysis.
  • Analysis of pathological consequences of APA dysregulation in cancer.

Main Results:

  • APA generates mRNA diversity, crucial for gene expression regulation.
  • RBPs are central regulators of APA, influencing mRNA isoform production.
  • Aberrant APA events contribute to tumor heterogeneity and cancer progression.
  • APA dysregulation impacts cell proliferation, invasion, metastasis, and therapy response.

Conclusions:

  • APA and RBPs play critical roles in normal cellular processes and disease, particularly cancer.
  • Targeting APA machinery and RBPs offers potential for novel cancer diagnostics and therapeutics.
  • Further research into APA-RBP interactions can lead to innovative treatment strategies for various cancers.
Keywords:
3' UTRAPARNA binding proteincancer

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