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Updated: Jul 20, 2025

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Physical interaction between STAT3 and AP1 in cervical carcinogenesis: Implications in HPV transcription control

Kulbhushan Thakur1, Divya Janjua1, Nikita Aggarwal1

  • 1Molecular Oncology Laboratory, Department of Zoology, University of Delhi (North Campus), New Delhi, India.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|August 2, 2023
PubMed

Insights

Signal Transducer and Activator of Transcription 3 (STAT3) indirectly interacts with HPV DNA via c-FOS and c-JUN in cervical cancer. This interaction influences viral oncoprotein expression and affects patient prognosis.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Constitutive activation of Signal Transducer and Activator of Transcription 3 (STAT3) is implicated in cervical cancer (CaCx) progression.
  • The precise mechanisms by which STAT3 influences Human Papillomavirus (HPV) transcription remain unclear.

Purpose of the Study:

  • To investigate the direct and indirect interactions between STAT3 and the HPV16/18 Long Control Region (LCR).
  • To elucidate the role of STAT3 in regulating viral oncoprotein expression and its impact on CaCx prognosis.

Main Methods:

  • In silico analysis of STAT3 binding motifs on HPV LCR.
  • Chromatin immunoprecipitation (ChIP-PCR) to validate STAT3 binding.
  • Co-immunoprecipitation and immunocytochemistry to assess protein-protein interactions.
  • Proximity ligation assay to confirm STAT3-AP1 complex formation.
  • Analysis of STAT3 and c-JUN expression in CaCx tumor tissues.

Main Results:

  • STAT3 does not directly bind to the HPV16 LCR.
  • STAT3 physically interacts with c-FOS and c-JUN, forming a complex with AP1.
  • IL-6 treatment enhances STAT3/c-FOS/c-JUN colocalization, while Stattic treatment reduces it.
  • Altered STAT3 expression impacts c-FOS/c-JUN localization and viral oncoprotein (E6/E7) expression.
  • High c-JUN expression correlates with poor prognosis in HPV16/18 CaCx; high STAT3 correlates with poor prognosis in HPV18 CaCx.

Conclusions:

  • STAT3 indirectly interacts with HPV LCR through c-FOS and c-JUN.
  • This indirect interaction potentiates the transcription of viral oncoproteins, contributing to CaCx development.
  • STAT3 and c-JUN expression levels serve as potential prognostic biomarkers for cervical cancer.
Keywords:
Activator protein 1 (AP1)Cervical cancer (CaCx)Human papillomavirus (HPV)Long control region (LCR)Signal transducer and activator of transcription 3 (STAT3)

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