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Background <p>Sex-determining region Y-box 12 (<i>SOX12</i>), a key member of the SOXC transcription factor subfamily, exerts oncogenic roles in multiple malignancies via its conserved HMG-box DNA-binding domain. Although existing studies have reported its abnormal expression and functional implications in various tumors, previous reviews lack a systematic summary of <i>SOX12</i>-mediated regulatory networks across cancers, failing to address research gaps and potential therapeutic targets.</p> Main body <p>This review comprehensively summarizes <i>SOX12</i>’s expression patterns and oncogenic functions in digestive, reproductive, hematologic, and other tumor types. We systematically dissect its core molecular mechanisms, including competing endogenous RNA (ceRNA) networks, activation of canonical signaling pathways (e.g. <i>PI3K</i>/<i>AKT</i>/<i>mTOR</i>, <i>Wnt</i>/<i>β-catenin</i>), metabolic reprogramming, and modulation of the tumor immune microenvironment. Additionally, we highlight <i>SOX12</i>’s clinical potential as a prognostic biomarker and therapeutic target, discussing novel targeting strategies such as HMG-box domain inhibitors and ceRNA network intervention.</p> Conclusions <p><i>SOX12</i> serves as a critical “metabolic-immune” cross-regulatory node in tumors, with conserved oncogenic mechanisms across cancer types. Its abnormal expression is closely associated with malignant phenotypes and poor prognosis, supporting its dual value as a prognostic indicator and therapeutic target. Future research should focus on exploring its post-translational modifications, synergistic mechanisms with other SOX family members, and conducting large-scale clinical trials to validate its translational potential.</p>

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The oncogenic potential of SOX12: a comprehensive and perspective view

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Haokun Leng,
  • Yuanqi Liu,
  • Lei Wu

摘要

Background

Sex-determining region Y-box 12 (SOX12), a key member of the SOXC transcription factor subfamily, exerts oncogenic roles in multiple malignancies via its conserved HMG-box DNA-binding domain. Although existing studies have reported its abnormal expression and functional implications in various tumors, previous reviews lack a systematic summary of SOX12-mediated regulatory networks across cancers, failing to address research gaps and potential therapeutic targets.

Main body

This review comprehensively summarizes SOX12’s expression patterns and oncogenic functions in digestive, reproductive, hematologic, and other tumor types. We systematically dissect its core molecular mechanisms, including competing endogenous RNA (ceRNA) networks, activation of canonical signaling pathways (e.g. PI3K/AKT/mTOR, Wnt/β-catenin), metabolic reprogramming, and modulation of the tumor immune microenvironment. Additionally, we highlight SOX12’s clinical potential as a prognostic biomarker and therapeutic target, discussing novel targeting strategies such as HMG-box domain inhibitors and ceRNA network intervention.

Conclusions

SOX12 serves as a critical “metabolic-immune” cross-regulatory node in tumors, with conserved oncogenic mechanisms across cancer types. Its abnormal expression is closely associated with malignant phenotypes and poor prognosis, supporting its dual value as a prognostic indicator and therapeutic target. Future research should focus on exploring its post-translational modifications, synergistic mechanisms with other SOX family members, and conducting large-scale clinical trials to validate its translational potential.