期刊
AGING-US
卷 12, 期 8, 页码 6756-6773出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103036
关键词
tongue squamous cell carcinoma; docetaxel; chemoresistance; miR-200c; TUBB3; PPP2R1B
Background: Chemoresistance is the main challenge for treating tongue squamous cell carcinoma (TSCC). MiR-200c is an important regulator of chemoresistance. Exosomes are a promising molecule-delivery system for cancer treatment. Thus, this study aimed to investigate the role of miR-200c in chemoresistance of TSCC and whether exosomes could effectively deliver miR-200c to chemo-resistant cells and regulate cellular activities. Results: The results showed that the downregulation of miR-200c increased resistance to DTX, migration, and invasion and decreased apoptosis, which was reversed by the overexpression of miR-200c. The NTECs-derived exosomes transported miR-200c to HSC-3DR, increasing the sensitivity to DTX in vitro and in vivo. Also, epithelial-to-mesenchymal transition (EMT) and DNA damage responses were involved in DTX resistance. Furthermore, miR-200c regulated DTX resistance by targeting TUBB3 and PPP2R1B. Conclusion: Exosome-mediated miR-200c delivery may be an effective and promising strategy to treat chemoresistance in TSCC. Methods: Docetaxel (DTX) resistant HSC-3 cells (HSC-3DR) were transfected with miR-200c lentivirus and cocultured with exosomes derived from normal tongue epithelial cells (NTECs) that were overexpressed with miR-200c. The roles of miR-200c and exosomal miR-200c in vitro and in vivo were determined by RNA-Seq, qRT-PCR, western blots, transmission electron microscopy, and flow cytometry, fluorescence, CCK8, Transwell, and wound healing assays.
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