Epigallocatechin‐3‐gallate inhibited cancer stem cell–like properties by targeting hsa‐mir‐485‐5p/RXRα in lung cancer

Non–small‐cell lung cancer (NSCLC) appears to be a significant threat to public health worldwide. MicroRNAs have been identified as significant regulators for the development of NSCLC. Previous reports have suggested that hsa‐mir‐485‐5p is dysregulated in various cancers. RXRα, as a kind of nuclear receptor, is an effective target of cancer treatment. Cancer stem cells (CSCs) are recognized as the main cause for tumor metastasis, recurrence, and chemotherapy resistance. However, the mechanism by which hsa‐mir‐485‐5p and RXRα modulate CSCs in NSCLC remains unknown. Here, we found that hsa‐mir‐485‐5p was decreased in serum samples from patients with NSCLC and NSCLC cells. Meanwhile, epigallocatechin‐3‐gallate (EGCG), an effective anticancer compound extracted from green tea, can enhance hsa‐mir‐485‐5p expression. Hsa‐mir‐485‐5p mimics markedly inhibited NSCLC cell growth and induced cell apoptosis. However, inhibition of hsa‐mir‐485‐5p significantly enriched CSC‐like traits. Moreover, bioinformatics analysis predicted the binding correlation between hsa‐mir‐485‐5p and RXRα, which was confirmed by a dual‐luciferase reporter assay. We observed that RXRα was increased in NSCLC and EGCG could inhibit RXRα levels dose dependently. In addition, RXRα upregulation or activation expanded the CSC‐like properties of NSCLC cells, whereas RXRα inhibition or inactivation could exert a reverse phenomenon. Consistently, in vivo experiments also validated that EGCG could repress the CSC‐like characteristics by modulating the hsa‐mir‐485‐5p/RXRα axis. Our findings may reveal a novel molecular mechanism for the treatment of NSCLC. Epigallocatechin‐3‐gallate inhibited the cancer stem cell–like properties of non–small‐cell lung cancer (NSCLC). hsa‐mir‐485‐5p inhibited the stemness of NSCLC. RXRα can act as a target of hsa‐mir‐485‐5p.