Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer
10.1016/j.jpha.2024.101118
- Author:
Meirong ZHOU
1
;
Jiayue WANG
;
Yulin PENG
;
Xiangge TIAN
;
Wen ZHANG
;
Junlin CHEN
;
Yue WANG
;
Yu WANG
;
Youjian YANG
;
Yongwei ZHANG
;
Xiaokui HUO
;
Yuzhuo WU
;
Zhenlong YU
;
Tian XIE
;
Xiaochi MA
Author Information
1. Second Affiliated Hospital,Dalian Medical University,Dalian,Liaoning,116000,China;Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention,College of Integrative Medicine,Dalian Medical University,Dalian,Liaoning,116044,China
- Publication Type:Journal Article
- Keywords:
Elemene;
Inflammatory;
Nuclear factor kappaB;
microRNA-145-5p;
Non-small cell lung cancer
- From:
Journal of Pharmaceutical Analysis
2025;15(3):585-598
- CountryChina
- Language:English
-
Abstract:
Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.
