RBM3 suppresses stemness remodeling of prostate cancer in bone microenvironment by modulating N6-methyladenosine on

Shouyi Zhang1, Chengcheng Lv1, Yichen Niu2

  • 1Department of Urology, the Cancer Hospital of Dalian University of Technology & Liaoning Cancer Hospital, Shenyang, Liaoning, 110042, China.

Cell Death & Disease
|February 7, 2023
PubMed

Insights

RNA binding motif 3 (RBM3) protein inhibits prostate cancer (PCa) bone metastasis by decreasing cancer stemness. RBM3 upregulates m6A methylation of CTNNB1 mRNA, reducing its stability and inactivating Wnt signaling.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Bone metastasis is a critical challenge in prostate cancer (PCa) treatment.
  • The bone microenvironment can induce cancer cell adaptation and stemness, promoting secondary metastasis.
  • RNA binding motif 3 (RBM3) is known to influence PCa stem cell properties.

Purpose of the Study:

  • To investigate the role of RBM3 in resisting microenvironmental remodeling of PCa during bone metastasis.
  • To elucidate the molecular mechanism by which RBM3 affects PCa cell stemness in the bone metastatic setting.

Main Methods:

  • Co-culturing PCa cells with osteoblasts to simulate the bone metastatic microenvironment.
  • Assessing the impact of RBM3 on N6-methyladenosine (m6A) methylation of CTNNB1 mRNA.
  • Evaluating the effect of RBM3-mediated CTNNB1 modification on Wnt signaling pathway activity and cancer stemness.

Main Results:

  • RBM3 upregulates m6A methylation of catenin beta 1 (CTNNB1) mRNA in a METTL3-dependent manner.
  • This m6A modification leads to decreased CTNNB1 mRNA stability.
  • Consequently, Wnt signaling is inactivated, inhibiting osteoblast-induced stemness remodeling in PCa cells.

Conclusions:

  • RBM3 acts as a suppressor of PCa stemness in the bone metastatic niche.
  • RBM3 inhibits PCa bone metastasis by downregulating CTNNB1 mRNA stability and Wnt signaling.
  • This study expands the understanding of RBM3's inhibitory role in prostate cancer bone metastasis.

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