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Updated: Nov 2, 2025
Biotin-based Pulldown Assay to Validate mRNA Targets of Cellular miRNAs
Published on: June 12, 2018
WBP2 inhibits microRNA biogenesis via interaction with the microprocessor complex
Hossein Tabatabaeian1,2, Shen Kiat Lim1,3, Tinghine Chu1,4
1Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Abstract:
WBP2 is an emerging oncoprotein with diverse functions in breast tumorigenesis via regulating Wnt, epidermal growth factor receptor, estrogen receptor, and Hippo. Recently, evidence shows that WBP2 is tightly regulated by the components of the miRNA biogenesis machinery such as DGCR8 and Dicer via producing both WBP2's 3'UTR and coding DNA sequence-targeting miRNAs. This led us to hypothesize that WBP2 could provide a feedback loop to the biogenesis of its key upstream regulators by regulating the microprocessor complex activity. Indeed, WBP2 suppressed microprocessor activity by blocking the processing of pri-miRNAs to pre-miRNAs. WBP2 negatively regulated the assembly of the microprocessor complex via physical interactions with its components. Meta-analyses suggest that microprocessor complex components, in particular DGCR8, DDX5, and DEAD-Box Helicase17 (DDX17), have tumor-suppressive properties. 2D and 3D in vitro proliferation assays revealed that WBP2 blocked the tumor-suppressive properties of DGCR8, a key component of the microprocessor complex. In conclusion, WBP2 is a novel regulator of miRNA biogenesis that is a known dysregulated pathway in breast tumorigenesis. The reregulation of miRNA biogenesis machinery via targeting WBP2 protein may have implications in breast cancer therapy.
Insights
WBP2, a breast cancer oncoprotein, suppresses microRNA (miRNA) biogenesis by inhibiting the microprocessor complex. This finding suggests targeting WBP2 could be a new therapeutic strategy for breast cancer.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- WBP2 is an oncoprotein implicated in breast cancer, influencing pathways like Wnt and estrogen signaling.
- WBP2 is regulated by microRNA (miRNA) biogenesis machinery, including DGCR8 and Dicer.
- Microprocessor complex components, such as DGCR8, DDX5, and DDX17, exhibit tumor-suppressive functions.
Purpose of the Study:
- To investigate the hypothesis that WBP2 regulates miRNA biogenesis machinery.
- To determine if WBP2 influences the activity of the microprocessor complex.
- To explore the interaction between WBP2 and the tumor-suppressive functions of DGCR8.
Main Methods:
- In vitro assays to assess WBP2's effect on pri-miRNA to pre-miRNA processing.
- Co-immunoprecipitation to study physical interactions between WBP2 and microprocessor complex components.
- Cell proliferation assays (2D and 3D) to evaluate WBP2's impact on DGCR8's tumor-suppressive activity.
Main Results:
- WBP2 was found to suppress microprocessor activity, inhibiting pri-miRNA processing.
- WBP2 physically interacts with microprocessor complex components, negatively regulating its assembly.
- WBP2 blocks the tumor-suppressive properties of DGCR8 in proliferation assays.
Conclusions:
- WBP2 is a novel regulator of miRNA biogenesis, impacting a pathway crucial in breast tumorigenesis.
- WBP2's suppression of the microprocessor complex and its interaction with DGCR8 highlight a new feedback loop.
- Targeting WBP2 may offer a therapeutic avenue for breast cancer by restoring miRNA biogenesis regulation.
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