MiR-27b-3p facilitates non-small cell lung cancer cell ferroptosis through targeting SLC7A11

Rong Chen¹, Qingyu Zhou², Shuai Guo¹, Yahui Shen¹,^*

1. Department of Respiratory and Critical Care Medicine, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu 225300, China.
2. Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu 225300, China.

• Corresponding Author:Yahui Shen; E-mail: shenyahui@njmu.edu.cn

Abstract
Objective
To investigate the role of microRNA-27b-3p (miR-27b-3p) in regulating ferroptosis in non-small cell lung cancer (NSCLC) cells and to elucidate the underlying molecular mechanism, with a focus on its interaction with SLC7A11.
Methods
The expression levels of miR-27b-3p and SLC7A11 were examined in NSCLC cell lines. Gain-of-function experiments were performed by overexpressing miR-27b-3p to assess its effects on NSCLC cell proliferation, migration, invasion, apoptosis, and ferroptosis. Ferroptosis was evaluated by measuring intracellular free iron, lipid peroxidation, and reactive oxygen species (ROS) levels in erastin-treated NSCLC cells. The targeting relationship between miR-27b-3p and SLC7A11 was analyzed, and rescue experiments were conducted by overexpressing SLC7A11 in miR-27b-3p–overexpressing cells.
Results
miR-27b-3p expression was significantly downregulated, while SLC7A11 expression was upregulated in NSCLC cells. Overexpression of miR-27b-3p inhibited NSCLC cell proliferation, migration, and invasion, and enhanced apoptosis and ferroptosis, as indicated by increased free iron, lipid peroxidation, and ROS levels in erastin-treated cells. SLC7A11 was identified as a target of miR-27b-3p, and its overexpression reversed the inhibitory effects of miR-27b-3p on proliferation, migration, and invasion, as well as the promoting effects on apoptosis and ferroptosis in NSCLC cells.
Conclusion
miR-27b-3p acts as a tumor suppressor in NSCLC by inducing ferroptosis and inhibiting malignant behaviors of NSCLC cells through direct targeting and negative regulation of SLC7A11. These findings suggest that the miR-27b-3p/SLC7A11 axis may represent a potential therapeutic target for NSCLC.
Keywords: non-small cell lung cancer, ferroptosis, miR-27b-3p, SLC7A11