Cigarette Smoke Extract Promotes Epithelial-Mesenchymal Transition in Non-Small Cell Lung Cancer by Upregulating...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Non-small cell lung cancer (NSCLC) is a major global health concern.
• Cigarette smoke extract (CSE) is a significant risk factor for NSCLC, but its molecular drivers are not fully understood.
• Protein arginine methyltransferase 6 (PRMT6) and epithelial-mesenchymal transition (EMT) are linked to cancer progression, yet their role in CSE-induced NSCLC is unclear.

Purpose of the Study:

• To investigate the role of PRMT6 in CSE-induced NSCLC progression.
• To elucidate the molecular mechanisms by which CSE affects NSCLC, focusing on PRMT6 and EMT.
• To evaluate the therapeutic potential of targeting PRMT6 in CSE-exposed NSCLC.

Main Methods:

• In vitro assays using H1299 cells and in vivo subcutaneous xenograft models in nude mice were employed.
• Assays included CCK-8, wound healing, Transwell, immunofluorescence, qRT-PCR, and western blotting to assess cell behavior and molecular changes.
• Immunohistochemistry was used to evaluate tumor growth and molecular alterations.

Main Results:

• CSE exposure increased proliferation, migration, and invasion of H1299 cells and promoted tumor growth in vivo.
• CSE upregulated PRMT6, H3R2me2a, mesenchymal markers (N-cadherin, MMP2, MMP9, vimentin), and EMT-associated transcription factors (Snail, TWIST1).
• CSE also increased PI3K/Akt/mTOR pathway activation, and these effects were reversed by the PRMT6 inhibitor EPZ020411.

Conclusions:

• CSE promotes NSCLC progression via PRMT6 upregulation, leading to PI3K/Akt/mTOR activation and EMT.
• PRMT6 plays a critical role in CSE-induced NSCLC progression.
• PRMT6 inhibition presents a potential therapeutic strategy for NSCLC.