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

• DOI: 10.1016/j.jpha.2024.101118
• Publication Date: 2024-10-02T03:12:58Z
• Authors: Meirong Zhou; 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
• Keywords: Elemene; Stabilizer (aeronautics)

Elemene is widely recognized as an effective anti-cancer compound and 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 patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques subsequent biochemical validations such microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) pinpointed a critical target through which exerts anti-tumor effects. Interestingly, serves binding stabilizer miR-145-5p, demonstrating strong affinity (dissociation constant (K D) = 0.39 ± 0.17 μg/mL) preventing degradation both vitro vivo, while interfering with synthesis primary microRNA transcripts (pri-miRNAs) precursor miRNAs (pre-miRNAs). The stabilization miR-145-5p by resulted increased level miRNA, subsequently suppressing progression miR-145-5p/mitogen-activated protein kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide new perspective on revealing interaction patterns between drugs miRNAs.