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Updated: May 10, 2025

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells
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Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

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Transcriptome-scale analysis of functional alternative back-splicing events in colorectal cancer

Qianqian Ning1,2,3, Qian Jin1,2,3, Lei Zhao4

  • 1Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, 221004, Jiangsu, China.

Journal of Translational Medicine
|April 24, 2025
PubMed
Abstract

Insights

Alternative back-splicing (ABS) events are prevalent in colorectal cancer (CRC). Aberrantly expressed ABS circRNAs are linked to CRC tumorigenesis and patient survival, offering potential therapeutic targets.

Area of Science:

  • Molecular biology
  • Genomics
  • Cancer research

Background:

  • Circular RNAs (circRNAs) are formed by gene back-splicing.
  • Alternative back-splicing (ABS) can generate multiple circRNAs from a single gene.
  • The role of ABS events in colorectal cancer (CRC) carcinogenesis is largely unknown.

Purpose of the Study:

  • To characterize the landscape of ABS events in CRC.
  • To identify ABS events associated with CRC carcinogenesis and patient prognosis.
  • To investigate the functional roles of specific ABS circRNAs in CRC.

Main Methods:

  • Analysis of transcriptome sequencing data from 176 CRC samples.
  • Identification of differentially expressed ABS circRNAs between tumor and normal tissues.
  • Cox regression analysis for prognostic ABS events.
  • In vitro and in vivo functional assays for circXPO1 variants.

Main Results:

  • Identified 19,611 high-confidence circRNAs, with 91.1% being recurrent.
  • ABS circRNAs constitute 68.8% of all identified circRNAs, indicating prevalence.
  • 552 ABS circRNAs were aberrantly expressed and linked to cancer hallmarks.
  • 13 ABS circRNAs served as independent prognostic indicators for CRC survival.
  • circXPO1-2 inhibited CRC cell proliferation, migration, and invasion, unlike circXPO1-1.

Conclusions:

  • ABS events are prevalent in the CRC transcriptome.
  • Aberrantly expressed ABS circRNAs are closely associated with CRC tumorigenesis.
  • ABS circRNAs represent potential novel therapeutic targets for CRC with clinical benefit.
Keywords:
Alternative back-splicing eventCircXPO1Circular RNAColorectal cancer

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