Epigallocatechin‐3‐gallate inhibited cancer stem cell–like properties by targeting hsa‐mir‐485‐5p/RXRα in lung cancer
Autor: | Ming Zhou, Lijun Chen, Zahula Mariyam, Aochang Chen, Ijaz Ul Haq, Qing Feng, Xiaoyue Wu, Chuyue Xu, Pan Jiang |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Lung Neoplasms Down-Regulation Mice Nude Transfection Biochemistry Catechin Metastasis Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Cancer stem cell Carcinoma Non-Small-Cell Lung microRNA medicine Animals Anticarcinogenic Agents Humans Gene Silencing Lung cancer Molecular Biology Analysis of Variance Reporter gene Retinoid X Receptor alpha Chemistry Molecular Mimicry Cell Biology medicine.disease Xenograft Model Antitumor Assays Up-Regulation respiratory tract diseases body regions MicroRNAs HEK293 Cells 030104 developmental biology Nuclear receptor A549 Cells Apoptosis Gene Knockdown Techniques 030220 oncology & carcinogenesis Neoplastic Stem Cells Cancer research Signal Transduction |
Zdroj: | Journal of Cellular Biochemistry. 119:8623-8635 |
ISSN: | 1097-4644 0730-2312 |
DOI: | 10.1002/jcb.27117 |
Popis: | 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. |
Databáze: | OpenAIRE |
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