EMT-associated microRNAs and their roles in cancer stemness and drug resistance

Abstract

Epithelial-to-mesenchymal transition (EMT) is implicated in a wide array of malignant behaviors of cancers, including proliferation, invasion, and metastasis. Most notably, previou studies have indicated that both cancer stem-like properties and drug resistance were associated with EMT. Furthermore, microRNAs (miRNAs) play a pivotal role in the regulation of EMT phenotype, as a result, some miRNAs impact cancer stemness and drug resistance. Therefore, understanding the relationship between EMT-associated miRNAs and cancer stemness/drug resistance is beneficial to both basic research and clinical treatment. In this review, we preliminarily looked into the various roles that the EMT-associated miRNAs play in the stem-like nature of malignant cells. Then, we reviewed the interaction between EMT-associated miRNAs and the drug-resistant complex signaling pathways of multiple cancers including lung cancer, gastric cancer, gynecologic cancer, breast cancer, liver cancer, colorectal cancer, pancreatic cancer, esophageal cancer, and nasopharyngeal cancer. We finally discussed the relationship between EMT, cancer stemness, and drug resistance, as well as looked forward to the potential applications of miRNA therapy for malignant tumors.

Keywords: cancer; cancer stem cell; cancer stemness; drug resistance; epithelial-to-mesenchymal transition; microRNA.

FIGURE 1

The relationship between EMT, stemness, and drug resistance. On one hand, the cancer cells harboring EMT phenotype may transform into drug‐resistant cells after long‐term therapy. On the other hand, the EMT may induce the generation of CSCs, which may go through a process of differentiation. Then the differentiated cells have the potential heterogeneity of being resistant to drug. Furthermore, EMT can generate the distant metastasis of cancer cells through the approaches of intravasation and extravasation