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The role of chimeric FAM72B transcripts generated by intergenic mRNA trans-splicing in breast cancer

Gangotri Patra1, Pok-Son Kim2, Arne Kutzner3

  • 1Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul, 04763, Republic of Korea.

Functional & Integrative Genomics
|December 2, 2025
PubMed

Insights

Novel chimeric ADIPOR2::FAM72B mRNA, formed by trans-splicing, drives cancer cell proliferation. These fusion transcripts are promising diagnostic and therapeutic targets for breast cancer.

Area of Science:

  • Genomics and Cancer Biology
  • Molecular Oncology
  • Gene Expression Regulation

Background:

  • The functional roles of the Family with sequence similarity 72 (FAM72) gene family in cancer are not fully understood.
  • Chimeric messenger RNAs (mRNAs) generated by intergenic mRNA trans-splicing (CRTS) are emerging as significant players in cancer biology.
  • Aging-related diseases, including various cancers, pose substantial societal threats, necessitating research into their underlying molecular mechanisms.

Purpose of the Study:

  • To investigate the functional significance of chimeric FAM72 fusion genes in cancer cell proliferation.
  • To explore the role of intergenic mRNA trans-splicing involving FAM72 in cancer.
  • To identify novel chimeric FAM72 fusion genes and their oncogenic potential.

Main Methods:

  • Biocomputational analyses were employed to detect chimeric FAM72 fusion genes across diverse cancer tissues.
  • Whole-genome sequencing (WGS) and next-generation sequencing of mRNA (RNA-seq) were utilized to identify genomic structural variants (SVs) and trans-splicing events.
  • A breast cancer tissue-specific cell system was established to assess the impact of chimeric transcripts on cancer cell proliferation and migration.

Main Results:

  • The study identified novel chimeric adiponectin receptor-2 (ADIPOR2)::FAM72B mRNA transcripts, predominantly generated via intergenic mRNA trans-splicing.
  • Expression of these chimeric ADIPOR2::FAM72B mRNA fusion transcripts was shown to enhance cancer cell proliferation and migration.
  • The identified chimeric transcripts were found to be associated with breast cancer tissues.

Conclusions:

  • The novel chimeric ADIPOR2::FAM72B mRNAs, resulting from intergenic mRNA trans-splicing, function as oncogenic drivers.
  • These chimeric transcripts represent potential diagnostic biomarkers and therapeutic targets for breast cancer.
  • Further research into FAM72-related trans-splicing events could uncover new avenues for cancer treatment.
Keywords:
CancerCell cycleChimeric mRNAFusion geneProliferation

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