AI Article Synopsis
- Cancer stem cells (CSCs) are key players in tumor growth, spread, and recurrence, making them important targets for cancer treatment.
- The study reveals that the interaction of miR-135a and SMYD4 triggers the conversion of non-CSCs to CSCs by enhancing Nanog expression and modifying DNA methylation.
- Targeting the miR-135a/DNMT1 and SMYD4 pathways may offer new strategies for effective CSC-targeted therapies.
Article Abstract
Cancer stem cells (CSCs) are the main cause of tumor development, metastasis, and relapse. CSCs are thus considered promising targets for cancer therapy. However, it is hard to eradicate CSCs due to their inherent plasticity and heterogeneity, and the underlying mechanism of the switch between non-CSCs and CSCs remains unclear. Here, it is shown that miR-135a combined with SMYD4 activates Nanog expression and induces the switch of non-CSCs into CSCs. The miR-135a level, once elevated, lowers the methylation level of the CG5 site in the promoter by directly targeting DNMT1. SMYD4 binds to the unmethylated promoter to activate Nanog expression in Nanog-negative tumor cells. The in vivo regulation of miR-135a levels could significantly affect both the CSCs proportion and tumor progression. These findings indicate that DNA methylation of the promoter modulates the switch of non-CSCs into CSCs under the control of the miRNA-135 level. In addition, the related pathways, miR-135a/DNMT1 and SMYD4, involved in these processes are potential targets for CSC-targeted therapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055559 | PMC |
| http://dx.doi.org/10.1002/advs.201903035 | DOI Listing |
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