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Updated: Aug 11, 2025

MicroRNA Detection in Prostate Tumors by Quantitative Real-time PCR qPCR
Published on: May 16, 2012
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.
Abstract:
Bone metastasis is the most happened metastatic event in prostate cancer (PCa) and needs a large effort in treatment. When PCa metastasizes to the bone, the new microenvironment can induce the epigenome reprogramming and stemness remodeling of cancer cells, thereby increasing the adaptability of cancer cells to the bone microenvironment, and this even leads to the occurrence of secondary tumor metastasis. Our group has previously found that RNA binding motif 3 (RBM3) affects the stem cell-like properties of PCa by interfering with alternative splicing of CD44. However, whether RBM3, as a stress-response protein, can resist microenvironmental remodeling of PCa particularly in bone metastasis remains unknown. By co-culturing PCa cells with osteoblasts to mimic PCa bone metastases, we found that RBM3 upregulates the N6-methyladenosine (m6A) methylation on the mRNA of catenin beta 1 (CTNNB1) in a manner dependent on methyltransferase 3 (METTL3), an N6-adenosine-methyltransferase complex catalytic subunit. Consequently, this modification results in a decreased stability of CTNNB1 mRNA and a followed inactivation of Wnt signaling, which ultimately inhibits the stemness remodeling of PCa cells by osteoblasts. Thus, the present study may extend our understanding of the inhibitory role of RBM3 on particularly bone metastasis of PCa.
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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