2. Academic Validation
  3. Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer

Elemene as a binding stabilizer of microRNA-145-5p suppresses the growth of non-small cell lung cancer

  • J Pharm Anal. 2025 Mar;15(3):101118. doi: 10.1016/j.jpha.2024.101118.
Meirong Zhou 1 2,  Jiayue Wang 1 2,  Yulin Peng 1 2,  Xiangge Tian 1,  Wen Zhang 1 2,  Junlin Chen 1 2,  Yue Wang 1,  Yu Wang 3,  Youjian Yang 3,  Yongwei Zhang 3,  Xiaokui Huo 1,  Yuzhuo Wu 1,  Zhenlong Yu 4,  Tian Xie 5,  Xiaochi Ma 1 2 6
Affiliations

Affiliations

  • 1 Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, 116000, China.
  • 2 Dalian Key Laboratory of Metabolic Target Characterization and Traditional Chinese Medicine Intervention, College of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 3 Research & Production Department, Dalian Huali Jingang Pharmaceutical Co., Ltd., Dalian, Liaoning, 116110, China.
  • 4 College of Pharmacy, Dalian Medical University, Dalian, Liaoning, 116044, China.
  • 5 Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, College of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, China.
  • 6 Shenzhen Bao'an Authentic TCM Therapy Hospital, Shenzhen, Guangdong, 518101, China.
PMID: 40161444 DOI: 10.1016/j.jpha.2024.101118
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. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K D) = 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 protein 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.

Keywords

Elemene; Inflammatory; Non-small cell lung cancer; Nuclear factor kappaB; microRNA-145-5p.

Figures
Products