Exosomal miR-522-3p Transferred from Cancer-associated Fibroblasts Promotes Lung Cancer Cell Progression via Regulating ZRANB2 Expression

Abstract

Objective: This study aimed to investigate the molecular insights by which microRNA (miR-522-3p) in cancer-associated fibroblast (CAF) derived exosomes regulate lung cancer cell growth, proliferation, and invasive capabilities. Method: CAFs and normal fibroblasts (NFs) were isolated from lung cancer and adjacent non-cancerous/normal tissues and identified. Exosomes secreted from CAFs and NFs were isolated to analyze their effects on lung cancer cell proliferation, migration, and invasion by Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assays. Next-generation sequencing (NGS) technology was applied to analyze microRNAs (miRNA) expression within the exosomes, specificaly measuring miR-522-3p. Additionally, a dual-luciferase reporter gene assay was utilized to validate the binding of zinc-finger RAN-binding domain-containing protein 2 (ZRANB2) to miR-522-3p. Results: The proliferation ability of cells in the CAF-exosomes (exo) groups significantly increased compared to NF-exo group (p < 0.05). Up-regulated miR-522-3p expression level was found in CAFs-exo (p < 0.001). Functional experiments demonstrated that miR-522-3p inhibitor can suppress lung cancer cell proliferation, migration, and invasion compared to the control inhibitor-exo groups (p < 0.05). ZRANB2 was a target gene of miR-522-3p. Conclusions: The present study highlights the role of CAFs in promoting lung cancer progression and metastasis via exosomal miR-522-3p, suggesting that the inhibition of CAF-derived miR-522-3p is an alternative modality for lung cancer treatment. These outcomes also provide a new perspective for further research on the lung cancer microenvironment and the development of treatment strategies.