The miRNA‐149‐5p/MyD88 axis is responsible for ursolic acid‐mediated attenuation of the stemness and chemoresistance of non‐small cell lung cancer cells

Autor: Chongxi Bao, Huasong Lu, Shuangqi Cai, Dongmei Liu, Jinliang Kong, Jin Luo, Cong Wu, Quanfang Chen
Rok vydání: 2020
Předmět:
Lung Neoplasms
Paclitaxel
Health
Toxicology and Mutagenesis
Paclitaxel resistance
Mice
Nude
010501 environmental sciences
Management
Monitoring
Policy and Law
Toxicology
Inhibitory postsynaptic potential
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Ursolic acid
Carcinoma
Non-Small-Cell Lung
Cell Line
Tumor
microRNA
medicine
Animals
Humans
Lung cancer
0105 earth and related environmental sciences
A549 cell
Mice
Inbred BALB C
Chemistry
General Medicine
respiratory system
medicine.disease
Xenograft Model Antitumor Assays
Triterpenes
respiratory tract diseases
Spheroid formation
Gene Expression Regulation
Neoplastic
MicroRNAs
A549 Cells
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Myeloid Differentiation Factor 88
Neoplastic Stem Cells
Cancer research
Non small cell
Zdroj: Environmental Toxicology. 35:561-569
ISSN: 1522-7278
1520-4081
DOI: 10.1002/tox.22891
Popis: Although the inhibitory roles of ursolic acid (UA) have been established in various tumors, its effects on the stemness of non-small cell lung cancer (NSCLC) cells are still unclear. Here, we constructed NSCLC cells with paclitaxel resistance (A549-PR) and showed that A549-PR exhibited a remarkably stronger stemness than the parental A549 cells, which is evident by the increase of spheroid formation capacity, stemness marker expression, and ALDH1 activity. Additionally, UA significantly reduced the stemness and paclitaxel resistance of A549-PR cells. Mechanistic investigations revealed that UA inhibited the miR-149-5p/MyD88 signaling, which is responsible for UA-mediated effects on the stemness of A549-PR cells. Notably, miR-149-5p/MyD88 axis promoted the stemness of A549 cells, while inhibition of this axis attenuated the stemness of A549-PR cells. Therefore, these results suggest that UA could attenuate the stemness and chemoresistance of NSCLC cells through targeting miR-149-5p/MyD88 axis.
Databáze: OpenAIRE
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