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Onconeural antigen NOVA1 dysregulates RNA alternative splicing in breast cancer

Daniel F Moakley1,2,3, Ye Wang1,2,3, Chaolin Zhang4,2,3

  • 1Department of Systems Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.

RNA (New York, N.Y.)
|June 3, 2026
PubMed

Insights

The neuron-specific splicing factor NOVA1, overexpressed in breast cancer, drives aberrant neuron-like splicing patterns, particularly in Luminal A tumors, impacting cell communication and movement pathways and potentially worsening prognosis.

Area of Science:

  • Oncology
  • Neuroscience
  • Molecular Biology

Background:

  • NOVA1, a neuron-specific splicing factor, is an onconeural antigen found in breast tumors.
  • While initially linked to tumor suppression via paraneoplastic neurological disorders (PNDs), NOVA1 also shows oncogenic activity in cell models.
  • Its role in mediating alternative splicing (AS) in native cancers was previously unclear.

Purpose of the Study:

  • To investigate the role of NOVA1 in mediating alternative splicing (AS) in breast invasive carcinoma (BRCA).
  • To determine if NOVA1 overexpression affects splicing patterns in cancer cells.
  • To associate NOVA1-mediated AS with specific breast tumor subtypes and patient prognosis.

Main Methods:

  • Analysis of alternative splicing (AS) profiles in breast invasive carcinoma (BRCA) tumor samples.
  • Examination of NOVA1 overexpression and its impact on gene splicing patterns.
  • Correlation analysis between NOVA1 expression, AS patterns, and Luminal A tumor subtype.

Main Results:

  • Aberrant NOVA1 overexpression activates neuron-like splicing patterns in BRCA, including brain-specific NOVA targets.
  • Splicing dysregulation affects genes involved in cell periphery, cytoskeleton, cell-cell communication, and neuronal functions.
  • NOVA1-mediated AS is most prominent in Luminal A tumors, with high NOVA1 expression linked to poorer prognosis.

Conclusions:

  • Ectopic NOVA1 in tumors exhibits regulatory activity impacting pathways crucial for tumor progression.
  • NOVA1-driven splicing alterations contribute to cancer development and progression, particularly in Luminal A breast cancer.
  • Understanding NOVA1's oncogenic splicing role offers potential therapeutic targets for breast cancer.
Keywords:
NOVA1RNA-binding proteinsalternative splicingcancer

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