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

作者：Zhu, Shan; Yang, Ning; Niu, Chao; Wang, Wan; Wang, Xue; Bai, Junge; Qiao, Yuan; Deng, Shuanglin; Guan, Yi; Chen, Jingtao^*

来源：Pharmacological Research, 2022, 179: 106196.

DOI：10.1016/j.phrs.2022.106196

• Chemoresistance
• MMP1
• miR-145
• Methylation
• Stemness

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 addi-tion, IMQ downregulated miR-145 by promoting DNA methylation at its promoter. DNA methyltransferase in-hibitors 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.

• 单位
  哈尔滨医科大学; 吉林大学