The miR-145–MMP1 axis is a critical regulator for imiquimod-induced cancer stemness and chemoresistance

Cancer stemness, chemoresistance, and metastasis are related biological events. However, whether they have common molecular mechanisms remains to be determined. Here, we report that imiquimod (IMQ) facilitates the acquisition of stem-cell-like properties and chemoresistance via the upregulation of m...

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Published in:Pharmacological research 2022-05, Vol.179, p.106196-106196, Article 106196
Main Authors: Zhu, Shan, Yang, Ning, Niu, Chao, Wang, Wan, Wang, Xue, Bai, Junge, Qiao, Yuan, Deng, Shuanglin, Guan, Yi, Chen, Jingtao
Format: Article
Language:English
Subjects:
Cell Line, Tumor
Cell Proliferation
Chemoresistance
Drug Resistance, Neoplasm - genetics
Gene Expression Regulation, Neoplastic
Imiquimod - pharmacology
Matrix Metalloproteinase 1 - genetics
Matrix Metalloproteinase 1 - metabolism
Matrix Metalloproteinase 1 - pharmacology
Methylation
MicroRNAs - genetics
MicroRNAs - metabolism
miR-145
MMP1
Neoplasms - drug therapy
Neoplasms - genetics
Stemness
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Summary:Cancer stemness, chemoresistance, and metastasis are related biological events. However, whether they have common molecular mechanisms remains to be determined. Here, we report that imiquimod (IMQ) facilitates the acquisition of stem-cell-like properties and chemoresistance via the upregulation of matrix metalloproteinase 1 (MMP1) and downregulation of microRNA-145 (miR-145). MiR-145–5p was found to suppress MMP1 expression through direct binding, and miR-145-mediated downregulation of MMP1 reversed the effects of IMQ. In addition, IMQ downregulated miR-145 by promoting DNA methylation at its promoter. DNA methyltransferase inhibitors limited IMQ-induced MMP1 expression, stemness, and chemoresistance. Collectively, our results highlight the miR-145–MMP1 axis as a potential coordinator of cancer stemness and chemoresistance. Given the role of MMP1 in the initiation of metastasis, the miR-145–MMP1 axis serves as a promising therapeutic target for improved cancer treatment. [Display omitted] •IMQ facilitates the acquisition of stem cell-like properties and chemoresistance.•IMQ upregulates MMP1 and downregulates miR-145 in cancer cells.•miR-145–5p directly suppresses MMP1 expression in a dual UTR interaction manner.•miR-145-mediated MMP1 downregulation reverses the effects of IMQ.•IMQ downregulates miR-145 by promoting DNA methylation at its promoter.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2022.106196