The crosstalk between microRNAs and the Wnt/β-catenin signaling pathway in cancer
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Updated: Mar 12, 2026

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Published on: October 27, 2014
Yin Peng1,2, Xiaojing Zhang1,3, Xianling Feng1
1Department of Pathology, The Shenzhen University School of Medicine, Shenzhen, Guangdong, People's Republic of China.
Abstract:
Mounting evidence has indicated microRNA (miR) dysregulation and the Wnt/β-catenin signaling pathway jointly drive carcinogenesis, cancer metastasis, and drug-resistance. The current review will focus on the role of the crosstalk between miRs and the Wnt/β-catenin signaling pathway in cancer development. MiRs were found to activate or inhibit the canonical Wnt pathway at various steps. On the other hand, Wnt activation increases expression of miR by directly binding to its promoter and activating transcription. Moreover, there are mutual feedback loops between some miRs and the Wnt/β-catenin signaling pathway. Clinical trials of miR-based therapeutic agents are investigated for solid and hematological tumors, however, challenges concerning low bioavailability and possible side effects must be overcome before the final clinical application. This review will describe current understanding of miR crosstalk with the Wnt/β-catenin signaling cascade. Better understanding of the regulatory network will provide insight into miR-based therapeutic development.
Insights
MicroRNA (miR) and Wnt/β-catenin pathway crosstalk drives cancer development and drug resistance. Understanding this complex network is key for developing novel miR-based cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- MicroRNA (miR) dysregulation is implicated in cancer.
- The Wnt/β-catenin signaling pathway is crucial in cell proliferation and cancer.
- Crosstalk between miRs and Wnt/β-catenin signaling contributes to carcinogenesis, metastasis, and drug resistance.
Purpose of the Study:
- To review the intricate crosstalk between miRs and the Wnt/β-catenin signaling pathway in cancer.
- To elucidate the mechanisms by which miRs and Wnt/β-catenin signaling interact.
- To highlight the therapeutic potential and challenges of targeting this network.
Main Methods:
- Literature review of studies investigating miR and Wnt/β-catenin pathway interactions in cancer.
- Analysis of molecular mechanisms of activation and inhibition.
- Examination of feedback loops and clinical trial data.
Main Results:
- MiRs can activate or inhibit the canonical Wnt pathway at multiple steps.
- Wnt pathway activation can increase miR expression via direct promoter binding.
- Mutual feedback loops exist between specific miRs and the Wnt/β-catenin pathway.
Conclusions:
- The complex interplay between miRs and Wnt/β-catenin signaling is a significant driver of cancer.
- Targeting this regulatory network offers potential for novel cancer therapeutics.
- Overcoming challenges like bioavailability and side effects is crucial for clinical application of miR-based therapies.
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