hnRNPC regulates cancer-specific alternative cleavage and polyadenylation profiles

Harry Fischl1, Jonathan Neve1, Zhiqiao Wang1

  • 1Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.

Insights

Alternative cleavage and polyadenylation (APA) generates distinct mRNA profiles in colon cancer progression. Overexpression of hnRNPC drives metastatic cancer cell APA profiles, impacting cancer-related genes like MTHFD1L.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • Alternative cleavage and polyadenylation (APA) expands the mRNA isoform repertoire, influencing gene expression.
  • Deregulation of APA is linked to diseases, including cancer progression, but its role in cancer-specific isoform generation is unclear.

Purpose of the Study:

  • To investigate how APA generates cancer-specific isoform profiles during colon cancer progression.
  • To determine the physiological consequences of these APA profiles.

Main Methods:

  • Utilized a subcellular fractionation approach.
  • Analyzed nuclear and cytoplasmic APA profiles across successive stages of colon cancer using a cell line model.

Main Results:

  • Demonstrated the establishment of specific APA profiles during cancer progression.
  • Identified hnRNPC overexpression as critical for APA profiles in metastatic colon cancer cells.
  • Showed hnRNPC regulates poly(A) site selection in cancer-associated genes, including MTHFD1L.

Conclusions:

  • APA plays a significant role in shaping gene expression during colon cancer progression.
  • hnRNPC is a key regulator of APA in metastatic colon cancer, affecting genes vital for cancer development.

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