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

Jun Cui¹, Haiyan Wang², Xiaohe Zhang³, Xiaodong Sun³, Jin Zhang³, Jinji Ma³

¹Department of Dental Implantology, Jinan Stomatological Hospital, Jinan 250001, Shandong Province, China
²Department of Ultrasound, Shandong Provincial Qianfoshan Hospital, The First Hospital Affiliated with Shandong First Medical University, Jinan 250014, Shandong Province, China
³Department of Oral Disease Gaoxin Branch, Jinan Stomatological Hospital, Jinan 250001, Shandong Province, China

* Co-first author

Received: December 21, 2019Accepted: March 30, 2020Published: April 20, 2020

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.