http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Yulu Sun,Guijun Hao,Mengqi Zhuang,Huijuan Lv,Chunhong Liu,Keli Su 연세대학교의과대학 2022 Yonsei medical journal Vol.63 No.3
Purpose: Long non-coding RNAs (lncRNAs) may act as oncogenes in small-cell lung cancer (SCLC). Exosomes containing lncRNAsreleased from cancer-associated fibroblasts (CAF) accelerate tumorigenesis and confer chemoresistance. This studyaimed to explore the action mechanism of the CAF-derived lncRNA maternally expressed gene 3 (MEG3) on cisplatin (DDP) chemoresistanceand cell processes in SCLC. Materials and Methods: Quantitative real-time PCR was conducted to determine the expression levels of MEG3, miR-15a-5p, andCCNE1. Cell viability and metastasis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide andinvasion assays, respectively. A xenograft tumor model was developed to confirm the effect of MEG3 overexpression on SCLC progressionin vivo. Relationships between miR-15a-5p and MEG3/CCNE1 were predicted using StarBase software and validated bydual luciferase reporter assay. Western blotting was used to determine protein levels. A co-culture model was established to explorethe effects of exosomes on MEG3 expression in SCLC cell lines. Results: MEG3 was overexpressed in SCLC tissues and cells. MEG3 silencing significantly repressed cell viability and metastasis inSCLC. High expression of MEG3 was observed in CAF-derived conditioned medium (CM) and exosomes, and promoted chemoresistanceand cancer progression. Additionally, MEG3 was found to serve as a sponge of miR-15a-5p to mediate CCNE1 expression. Overexpression of miR-15a-5p and knockout of CCNE1 reversed the effects of MEG3 overexpression on cell viability and metastasis. Conclusion: MEG3 lncRNA released from CAF-derived exosomes promotes DDP chemoresistance via regulation of a miR-15a-5p/CCNE1 axis. These findings may provide insight into SCLC therapy.