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CircMMP2(6,7) Cooperates with β-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone

Yingru Xu1,2, Xincheng Li1,3, Shuxia Zhang4

  • 1Molecular Diagnosis and Gene Testing Center, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.

Cancer Research
|November 14, 2023
PubMed

Insights

A novel circular RNA, circMMP2(6,7), promotes breast cancer bone metastasis by disrupting bone homeostasis. Inhibiting the PRMT5 protein complex effectively blocks this process, offering a new therapeutic target for bone metastasis.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Bone metastasis is a major cause of mortality in breast cancer patients.
  • Understanding the molecular mechanisms of breast cancer bone metastasis is crucial for developing effective treatments.

Purpose of the Study:

  • To identify novel molecular players involved in breast cancer bone metastasis.
  • To elucidate the mechanism by which circMMP2(6,7) promotes bone metastasis.
  • To evaluate the therapeutic potential of targeting the circMMP2(6,7)/β-catenin/PRMT5 complex.

Main Methods:

  • Identification and validation of circMMP2(6,7) in breast cancer tissues.
  • In vitro and in vivo assays to assess the role of circMMP2(6,7) in bone metastasis.
  • Mechanistic studies involving protein-protein interactions and gene expression analysis.
  • Pharmacological inhibition of PRMT5 using GSK591.

Main Results:

  • circMMP2(6,7) was significantly upregulated in bone metastatic breast cancer tissues and correlated with metastasis.
  • circMMP2(6,7) enhanced breast cancer cell metastasis to bone by inducing bone metastatic niche formation.
  • circMMP2(6,7) formed a complex with β-catenin and PRMT5, leading to the upregulation of S100A4 and LGALS3.
  • GSK591, a PRMT5 inhibitor, effectively suppressed circMMP2(6,7)/β-catenin/PRMT5 complex-mediated bone metastasis.

Conclusions:

  • circMMP2(6,7) plays a critical role in promoting breast cancer bone metastasis by disrupting bone homeostasis.
  • The circMMP2(6,7)/β-catenin/PRMT5 complex is a key driver of breast cancer bone metastasis.
  • PRMT5 is a promising therapeutic target for the treatment of breast cancer bone metastasis.

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