인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
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지원사업
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커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
Abstract Objectives Exosomally transferred circular RNAs (circRNAs) are critical in cancer. However, the study of exosomal circRNAs in glioma resistance remains limited. Here, we further investigated the function and mechanism of exosomal circular RNA NT5E (circNT5E) in temozolomide-resistant glioma cells (TMZ-GCs). Methods Exosomes were isolated from TMZ-GCs and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. CircNT5E, microRNA-153 (miR-153), and heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) levels were measured by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in TMZ-sensitive and TMZ-resistant GCs and in treated TMZ-GCs. In addition, the colocalization of circNT5E and miR-153 was confirmed by fluorescence in situ hybridization (FISH) and dual-luciferase reporter assays. Internalization of exosomes was observed by immunofluorescence staining. TMZ resistance, proliferation, and pAKTser473 protein levels were evaluated by a Cell Counting Kit-8 (CCK-8) assay, an EdU incorporation assay, and Western blotting, respectively. In addition, tumor growth was examined using a xenograft tumor model in nude mice. Results We first proved that circNT5E was highly abundant in exosomes derived from TMZ-GCs. Then, we discovered that circNT5E could serve as a miR-153 sponge. Finally, knockdown of circNT5E reduced TMZ resistance and cell proliferation and downregulated AKT ser473 phosphorylation by targeting miR-153 in TMZ-GCs. Moreover, our data revealed that exosomes derived from TMZ-GCs also had obvious effects on inducing the TMZ resistance and proliferation of GCs. Moreover, we revealed that the packaging of circNT5E into exosomes can be driven by hnRNP A1. Conclusions Collectively, our findings proved that exosomal circNT5E transferred in a manner mediated by hnRNPA1 could accelerate TMZ resistance by targeting miR-153 in GCs, indicating that exosomal circNT5E is a therapeutic target for TMZ-resistant glioma.
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