β-elemene promotes miR-127-3p maturation, induces NSCLCs autophagy, and enhances macrophage M1 polarization through exosomal communication

Xiahui Wu; Jie Wu; Tingting Dai; Qiangcheng Wang; Shengjie Cai; Xuehan Wei; Jing Chen; Ziyu Jiang

doi:10.1016/j.jpha.2024.03.002

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Xiahui Wu, Jie Wu, Tingting Dai, Qiangcheng Wang, Shengjie Cai, Xuehan Wei, Jing Chen, Ziyu Jiang. β-elemene promotes miR-127-3p maturation, induces NSCLCs autophagy, and enhances macrophage M1 polarization through exosomal communication[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.03.002

Citation:

Xiahui Wu, Jie Wu, Tingting Dai, Qiangcheng Wang, Shengjie Cai, Xuehan Wei, Jing Chen, Ziyu Jiang. β-elemene promotes miR-127-3p maturation, induces NSCLCs autophagy, and enhances macrophage M1 polarization through exosomal communication[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.03.002

Citation:

Xiahui Wu, Jie Wu, Tingting Dai, Qiangcheng Wang, Shengjie Cai, Xuehan Wei, Jing Chen, Ziyu Jiang. β-elemene promotes miR-127-3p maturation, induces NSCLCs autophagy, and enhances macrophage M1 polarization through exosomal communication[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.03.002

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β-elemene promotes miR-127-3p maturation, induces NSCLCs autophagy, and enhances macrophage M1 polarization through exosomal communication

doi: 10.1016/j.jpha.2024.03.002

a Department of Oncology, Lianyungang Hospital Affiliated to Xuzhou Medical University, Lianyungang, 222002, China;
b Department of Oncology, The First People's Hospital of Lianyungang, Lianyungang, 222002, China;
c Department of Digestive System, Pukou Hospital of Traditional Chinese Medicine, Nanjing, 210000, China;
d Department of Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210000, China;
e Department of Oncology, the Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, 210000, China;
f The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210028, China;
g Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China

Funds:

This work was supported by the National Natural Science Foundation of China under grant (No.81973525)

Traditional Chinese Medicine Development Project of Jiangsu Province under grant (ZT202112).

Received Date: Oct. 19, 2023
Accepted Date: Mar. 06, 2024
Rev Recd Date: Jan. 29, 2024

Abstract

Abstract

β-elemene has been observed to exert inhibitory effects on a multitude of tumors, primarily through multiple pathways such as the inhibition of cancer cell proliferation and the induction of apoptosis. The present study is designed to elucidate the role and underlying mechanisms of β-elemene in the therapeutic intervention of non-small cell lung cancer (NSCLC). Both in vitro and in vivo experimental models corroborate the inhibitory potency of β-elemene on NSCLCs. Our findings indicate that β-elemene facilitates the maturation of miR-127-3p by inhibiting CBX8. Functioning as an upstream regulator of MAPK4, miR-127-3p deactivates the Akt/mTOR/p70S6K pathway by targeting MAPK4, thereby inducing autophagy in NSCLCs. Additionally, β-elemene augments the packaging of miR-127-3p into exosomes via SYNCRIP. Exosomal miR-127-3p further stimulates M1 polarization of macrophages by suppressing ZC3H4. Taken together, the detailed understanding of the mechanisms through which β-elemene induces autophagy in NSCLCs and facilitates M1 polarization of macrophages provides compelling scientific evidence supporting its potential utility in NSCLC treatment.
- β-elemene,
- miR-127-3p,
- NSCLC,
- Akt/mTOR/p70S6K,
- MAPK4