Long noncoding RNA H19 acts as a miR-340-3p sponge to promote epithelial-mesenchymal transition by regulating YWHAZ expression in paclitaxel-resistant breast cancer cells
Autor: | Wenrui Wang, Sulian Chen, Henan Xu, Qingling Yang, Wei Peng, Zheng‐Yuan Dong, Xin‐Yu Wei, Cheng‐Xu Yue, Shuo Yang, Lei Yan, Changjie Chen |
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Rok vydání: | 2020 |
Předmět: |
Epithelial-Mesenchymal Transition
Paclitaxel Health Toxicology and Mutagenesis Apoptosis 010501 environmental sciences Management Monitoring Policy and Law Biology Toxicology 01 natural sciences Metastasis 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Humans Epithelial–mesenchymal transition Wnt Signaling Pathway 0105 earth and related environmental sciences Cell Proliferation Competing endogenous RNA Wnt signaling pathway General Medicine medicine.disease Antineoplastic Agents Phytogenic Long non-coding RNA Gene Expression Regulation Neoplastic MicroRNAs 14-3-3 Proteins Tumor progression Drug Resistance Neoplasm 030220 oncology & carcinogenesis embryonic structures YWHAZ Cancer research MCF-7 Cells Female RNA Long Noncoding Signal transduction |
Zdroj: | Environmental toxicologyREFERENCES. 35(9) |
ISSN: | 1522-7278 |
Popis: | Breast cancer (BC) is the leading cause of cancer-related death in women worldwide and one of the most prevalent malignancy. In recent years, increasing evidence had illuminated that long noncoding RNAs (lncRNAs) serve as critical factors in multiple tumor progression, including BC. Emerging references had indicated that the lncRNA H19 acts as significant roles in tumor progression and epithelial-mesenchymal transition (EMT). However, the underlying molecular mechanisms and biological roles of H19 in BC invasion, metastasis and EMT are still unclear. In this study, it was detected that the expression level of H19 was increased in BC paclitaxel-resistant (PR) cells subline (MCF-7/PR) in comparison with MCF-7 parental cells. In vitro, there were demonstrated that H19 overexpression promoted BC cells proliferation, metastasis, invasion and EMT procedures, and suppressed cells apoptosis. Whereas, H19 suppression resulted in the contrary biological effects. Besides, bioinformatics tools and dual-luciferase reporters assays indicated that miR-340-3p could act as a potential target gene of H19, the underlying mechanism studies proved that H19 could act as a competing endogenous RNA (ceRNA) via competitively binding miR-340-3p to promote BC cell proliferation, metastasis and EMT by regulating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) and potentiate the Wnt/β-catenin signaling in BC cells. In summary, our findings demonstrated that H19 could act as a ceRNA in BC progression, metastasis and EMT through modulating miR-340-3p/YWHAZ axis and activating the canonical Wnt/β-catenin signaling pathway, indicating that H19 might act as an underlying therapeutic target and prognostic biomarker for BC therapy. |
Databáze: | OpenAIRE |
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