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Active components of Salvia miltiorrhizae to regulate the changes of exosomal miRNA in human lung adenocarcinoma A549 cells and the effects of exosomes on HUVEC

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 09
Page:
1600-1607
Research Field:
Publishing date:

Info

Title:
Active components of Salvia miltiorrhizae to regulate the changes of exosomal miRNA in human lung adenocarcinoma A549 cells and the effects of exosomes on HUVEC
Author(s):
ZHENG Qi1; WANG Xueqian1; XUE Chao1; WANG Hanzhou2; LIU Shuo1; HOU Wei1
1.Oncology Department;2.Pneumology Department,Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China.
Keywords:
cryptotanshinone; Tanshinone IIA; non-small cell lung cancer; HUVEC; miRNA; exosome
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2024.09.005
Abstract:
Objective:To investigate the differential expression of cryptotanshinone and Tanshinone IIA on endogenous small non-coding RNA(miRNA) in exosomes secreted by human lung adenocarcinoma A549 cells.To observe the effect of exosomes on HUVEC cells and explore its mechanism.Methods:A549 cells at logarithmic growth stage were treated with 6 μg/mL cryptotanshinone and 4 μg/mL tanshinone IIA,respectively,and cultured in serum-free medium for 24 hours.Exosomes were extracted from the cell supernatant according to the instructions.High-throughput sequencing technology was used to detect miRNA expression in A549 cells of each group,and the obtained differential genes were analyzed by GO and KEGG.Exosomes of each group were added to HUVEC cells,and the inhibition and migration of exosomes of each group on HUVEC cells were detected by CCK-8 test and scratch test,CD31 gene and protein expression was detected in HUVEC cells.Results:Cryptotanshinone could up-regulate 109 miRNAs and down-regulate 78 miRNAs.Tanshinone IIA could up-regulate 35 miRNAs and down-regulate 40 miRNAs.The function and pathway enrichment analysis of the different miRNAs showed that the differential expression genes of cryptotanshinone and tanshinone IIA were mainly related to endocytosis,cancer pathway,MAPK signaling pathway,hippo signaling pathway,Wnt signaling pathway,microRNAs in cancer,Rap1 signaling pathway,and actin cytoskeleton regulation.The cell proliferation experiment showed that both the exosomes and cryptotanshinone treated-exosomes had significant inhibitory effects on the proliferation of HUVEC cells,and the inhibitory effect of cryptotanshinone treated-exosomes was significantly higher than that of exosomes.The cell scratch test showed that the mobility of all exosomes decreased significantly after exosomes were administered.After 48 h of exosomes,HUVEC mobility of both cryptotanshinone treated-exosomes and tanshinone IIA treated-exosomes was significantly lower than that of empty exosomes.Hsa-miR-1246 in exosomes of A549 cells treated with cryptotanshinone was significantly increased,while the gene and protein expression of CD31 in HUVEC cells treated with cryptotanshinone exosomes was significantly decreased.Conclusion:Cryptotanshinone and Tanshinone IIA have certain regulatory effects on miRNA in A549 exosomes,and the enrichment analysis is related to several cancer-related signaling pathways.Exosomes of A549 cells treated with cryptotanshinone and tanshinone IIA have inhibitory effects on HUVEC.The possible mechanism of inhibition of vascular endothelial cell proliferation by cryptotanshinone and tanshinone IIA from the perspective of exosomes is further explored,aiming to provide new ideas for the treatment of lung cancer.

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Memo

Memo:
National Natural Science Foundation of China（No.82104656，82004179）;国家自然科学基金资助项目（编号：82104656，82004179）；北京市自然科学基金资助项目（编号：7214294）;中央级公益性科研院所基本科研业务费专项资金（编号：ZZ15-YQ-024）
Last Update: 2024-03-29