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Published on: May 6, 2018
Extracellular vesicle-encapsulated microRNA-761 enhances pazopanib resistance in synovial sarcoma
Kumiko Shiozawa1, Ji Shuting1, Yusuke Yoshioka2
1Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Abstract:
The development of drug resistance in tumor cells leads to relapse and distant metastasis. Secreted microRNAs (miRNAs) enclosed in extracellular vesicles (EVs) can act as intercellular messengers. The objective of our study was to elucidate the role of secreted miRNAs to better understand the regulatory network underlying pazopanib-resistance in synovial sarcoma cells. We performed a comprehensive analysis of secreted miRNA abundance in pazopanib treated/untreated synovial sarcoma cells from four different cell lines (SYO-1, HS-SYII, 1273/99, and YaFuSS) using microarray technology, and discovered miR-761 in EVs as a potential biomarker of pazopanib-resistance in synovial sarcoma. Furthermore, we showed that miR-761 putatively targeted three proteins, thyroid hormone receptor interactor 6 (TRIP6), lamin A/C (LMNA), and NAD-dependent protein deacetylase sirtuin-3 (SIRT3). Knockdown of any of these proteins was shown in previous studies to confer increased resistance to chemotherapeutic agents. Our findings provide new insight into the potential role of miR-761, an EV-secreted miRNA from synovial sarcoma cells, making it a potential candidate for use in sarcoma therapy in the future.
Insights
Secreted microRNAs (miRNAs) in extracellular vesicles (EVs) can drive pazopanib resistance in synovial sarcoma. Researchers identified miR-761 as a potential biomarker and therapeutic target for overcoming drug resistance in sarcoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Drug resistance in tumor cells contributes to cancer relapse and metastasis.
- Secreted microRNAs (miRNAs) within extracellular vesicles (EVs) mediate intercellular communication.
- Understanding resistance mechanisms is crucial for developing effective cancer therapies.
Purpose of the Study:
- To investigate the role of secreted miRNAs in pazopanib resistance in synovial sarcoma.
- To identify potential miRNA biomarkers associated with pazopanib resistance.
- To elucidate the regulatory network involving secreted miRNAs in synovial sarcoma.
Main Methods:
- Comprehensive analysis of secreted miRNA abundance using microarray technology.
- Comparison of miRNA profiles in pazopanib-treated and untreated synovial sarcoma cell lines.
- Bioinformatic prediction of miRNA targets.
Main Results:
- miR-761 was identified as a potential biomarker for pazopanib resistance in synovial sarcoma.
- miR-761 is secreted via EVs from synovial sarcoma cells.
- miR-761 putatively targets TRIP6, LMNA, and SIRT3, proteins linked to chemotherapeutic resistance.
Conclusions:
- miR-761 plays a significant role in pazopanib resistance in synovial sarcoma.
- EV-secreted miR-761 represents a potential therapeutic target for overcoming resistance.
- Further research into miR-761 may lead to novel sarcoma treatment strategies.
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