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. RXR alpha, 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 RXR alpha 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 RXR alpha, which was confirmed by a dual-luciferase reporter assay. We observed that RXR alpha was increased in NSCLC and EGCG could inhibit RXR alpha levels dose dependently. In addition, RXR alpha upregulation or activation expanded the CSC-like properties of NSCLC cells, whereas RXR alpha 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/RXR alpha axis. Our findings may reveal a novel molecular mechanism for the treatment of NSCLC.