HMGB1 Protein Interactions in Prostate and Ovary Cancer Models Reveal Links to RNA Processing and Ribosome Biogenesis

Aida Barreiro-Alonso1,2,3,4, Mónica Lamas-Maceiras1,2,3, Lidia Lorenzo-Catoira1,2,3

  • 1EXPRELA Group, Centro de Investigaciones Científicas Avanzadas (CICA), University of A Coruña (UDC), 15008 A Coruña, Spain.

Cancers
|September 28, 2021
PubMed

Insights

High-mobility group box 1 (HMGB1) interacts with proteins involved in chromatin stability, transcription, and RNA processing in cancer cells. These HMGB1 interactions are dysregulated in ovarian and prostate tumors, impacting cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Proteomics

Background:

  • High-mobility group box 1 (HMGB1) is a nuclear protein with established roles in chromatin stability and transcription.
  • The full spectrum of HMGB1 interactions and their functional implications in cancer remain incompletely understood.

Purpose of the Study:

  • To identify and characterize the HMGB1 interactome in prostate and ovary cancer cell lines.
  • To investigate the functional significance of HMGB1 interactions in cancer progression.

Main Methods:

  • Affinity purification coupled with mass spectrometry (AP-MS) to identify HMGB1 interacting proteins.
  • Yeast-two-hybrid assays to validate specific protein-protein interactions.
  • Analysis of Pan-Cancer Atlas data to correlate gene expression with clinical outcomes.

Main Results:

  • The HMGB1 nuclear interactome includes proteins involved in chromatin stability, transcription, and novel roles in mRNA and rRNA processing.
  • Identified interactions between HMGB1 and the NuRD complex (specifically RBBP7), and between the septin and THOC complexes with Rab11.
  • Dysregulation of genes encoding HMGB1-interacting proteins in ovarian and prostate carcinomas was observed.
  • Silencing HMGB1 in PC-3 cells downregulated key regulators of ribosome biogenesis and RNA processing (BOP1, RSS1, UBF1, KRR1, LYAR).

Conclusions:

  • HMGB1 plays a significant role in RNA processing, beyond its known functions in chromatin and transcription.
  • Novel HMGB1 interaction networks involving the NuRD, septin, THOC, and Rab11 complexes were elucidated.
  • The identified HMGB1-interacting proteins and their dysregulation in cancer highlight potential therapeutic targets and prognostic markers for prostate and ovarian carcinomas.

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