miR-224-5p Suppresses Non-Small Cell Lung Cancer via IL6ST-Mediated Regulation of the JAK2/STAT3 Pathway.

Abstract

Background: Our study aimed to explore the specific functions and potential mechanisms of miR-224-5p in non-small cell lung cancer (NSCLC).

Methods: We first analyzed the expression of miR-224-5p in NSCLC patients and cell lines through the GEO database and qRT-PCR analysis. Then, we used MTT assays, wound healing assays, Transwell assays, and western blotting to evaluate the effects of miR-224-5p on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we used a xenograft tumor model to evaluate the effect of miR-224-5p on NSCLC tumor growth. Potential binding targets of miR-224-5p were further identified through the target prediction databases, and the relationships between miR-224-5p, its targets, and downstream signaling pathways were further verified using luciferase reporter gene assays and western blotting.

Results: The GEO database and qRT-PCR analysis indicated that miR-224-5p was significantly downregulated in NSCLC patients and cell lines. Functional assays indicated that inhibiting miR-224-5p could enhance the proliferation, migration, invasion, and EMT of NSCLC cells, as well as accelerate tumor growth. In contrast, overexpression of miR-224-5p inhibited these processes. We identified IL6ST (interleukin 6 signal transducer) as a binding target of miR-224-5p. We observed that miR-224-5p could bind to and inhibit IL6ST expression and JAK2/STAT3 signaling pathway, and the inhibition of NSCLC tumor growth and JAK2/STAT3 pathway by miR-224-5p could be reversed by IL6ST overexpression.

Conclusion: Our study demonstrated that miR-224-5p inhibited NSCLC by targeting IL6ST, thereby downregulating the JAK2/STAT3 signaling pathway.