Hypoxic tumor cell-derived small extracellular vesicle miR-152-3p promotes cervical cancer radioresistance through KLF15 protein
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Published:2023-11-07
Issue:1
Volume:18
Page:
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ISSN:1748-717X
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Container-title:Radiation Oncology
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language:en
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Short-container-title:Radiat Oncol
Author:
Zhou Junying,Lei Ningjing,Tian Wanjia,Guo Ruixia,Gao Feng,Fu Hanlin,Zhang Jing,Dong Shiliang,Chen Mengyu,Ma Qian,Li Yong,Chang Lei
Abstract
Abstract
Background
Radiotherapy is widely used in treating cervical cancer patients, however, radioresistance unavoidably occurs and seriously affects the treatment effect. It is well known that hypoxia plays an important role in promoting radioresistance in tumor microenvironment, yet our understanding of the effect of small extracellular vesicles miRNA on cervical cancer radiosensitivity in hypoxic environment is still limited.
Methods
Small extracellular vesicles extracted from hypoxic and normoxic cultured cervical cancer cells were evaluated for their effects on radioresistance. miR-152-3p was found to be a potential effector in hypoxia-derived extracellular vesicles by searching the GEO database. Its downstream substrate was confirmed by double luciferase report, which was KLF15. The role of miR-152-3p and KLF15 in regulating cervical cancer radioresistance was detected by cell activity assays. The findings were confirmed in vivo by animal models. The expression of miR-152-3p was quantified by qRT-PCR and its prognostic significance was evaluated.
Results
Hypoxic environment promoted the secretion of small extracellular vesicles, and reduced the apoptosis and DNA damage caused by radiation, accompanied by increased expression of small extracellular vesicles miR-152-3p from hypoxic cervical cancer cells. Furthermore, small extracellular vesicles miR-152-3p promoted Hela xenograft growth and reduced the radiosensitivity vivo. Mechanism studies revealed that KLF15 protein was the downstream target of miR-152-3p in regulating radioresistance.
Conclusion
Our findings suggest that small extracellular vesicles miR-152-3p affects the therapeutic effect of radiotherapy and holds potential as a biomarker or therapeutic target for cervical cancer prognosis and improving radiotherapy.
Funder
Henan Province Colleges and Universities Innovative Talent Support Program Henan Province Health Young and Middle-aged Discipline Leader Training Project Henan Province Young and Middle-aged Health Science and Technology Innovative Talent Training Project Central Plains Youth Top Talent Project High-level Talents Return to China for Research Funding Project
Publisher
Springer Science and Business Media LLC
Subject
Radiology, Nuclear Medicine and imaging,Oncology
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