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Research Paper Volume 12, Issue 8 pp 6756—6773
Exosomal miR-200c suppresses chemoresistance of docetaxel in tongue squamous cell carcinoma by suppressing TUBB3 and PPP2R1B
- 1 Department of Dental Implantology, Jinan Stomatological Hospital, Jinan 250001, Shandong Province, China
- 2 Department of Ultrasound, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan 250014, Shandong Province, China
- 3 Department of Oral Disease Gaoxin Branch, Jinan Stomatological Hospital, Jinan 250001, Shandong Province, China
Received: December 21, 2019 Accepted: March 30, 2020 Published: April 20, 2020
https://doi.org/10.18632/aging.103036How to Cite
Copyright © 2020 Cui et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.