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  2. PRMT5 Inhibition Enhances Therapeutic Efficacy of Cisplatin via Mediating miR-29b-3p-Mcl-1 Expression in Lung Adenocarcinoma

PRMT5 Inhibition Enhances Therapeutic Efficacy of Cisplatin via Mediating miR-29b-3p-Mcl-1 Expression in Lung Adenocarcinoma

  • Cell Biol Int. 2025 Feb 1. doi: 10.1002/cbin.12278.
Haichao Li 1 Jiangjiang Fan 1 Weiwei Shen 2 Yong Zhang 3 Ximing Zhu 1 Pei Li 1 Zhongping Gu 1 Pengyu Jing 1
Affiliations

Affiliations

  • 1 Department of Thoracic Surgery, The Second Affiliated Hospital, Air Force Medical University, Xi'an, Shaanxi Province, China.
  • 2 Department of Oncology, The Second Affiliated Hospital, Air Force Medical University, Xi'an, Shaanxi Province, China.
  • 3 Department of Pulmonary Medicine, Xijing Hospital, Air Force Medical University, Xi'an, Shaanxi Province, China.
Abstract

Cisplatin is one of the front-line therapeutic agents used to treat cancers, while drug resistance is a great obstacle to anti-tumor efficiency. Protein arginine methyltransferase 5 (PRMT5) has been identified as a promoter of tumorigenesis, motility, and invasion. Inhibiting PRMT5 reduced hypoxia-induced carboplatin resistance in lung adenocarcinoma (LUAD). However, the specific relationship between PRMT5 and cisplatin (CDDP) warrants further investigation. Our research revealed that PRMT5 Inhibitor C9 enhanced CDDP chemosensitivity by suppressing proliferation and promoting Apoptosis in LUAD cells. Through examining pro-apoptotic proteins regulated by PRMT5, we identified that Mcl-1 played a significant role in PRMT5-mediated CDDP chemosensitivity. Furthermore, PRMT5 regulated Mcl-1 expression through mediating miR-29b-3p. In vivo, our research presented that C9 increased CDDP chemosensitivity in LUAD xenografts. All in all, our data raised an interesting possibility that epigenetic reprogramming was associated with chemosensitivity. PRMT5 Inhibitor C9 improved CDDP effectiveness in LUAD cells by inhibiting Mcl-1 expression via miR-29b-3p, thereby modulating cellular proliferation and Apoptosis.

Keywords

Mcl‐1; PRMT5; apoptosis; cisplatin chemosensitivity; lung adenocarcinoma.

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