SET Domain-Containing Protein 5 Enhances the Cell Stemness of Non-Small Cell Lung Cancer via the PI3K/Akt/mTOR Pathway

Background: SET domain-containing protein 5 (SETD5) could promote non-small cell lung cancer (NSCLC) cell invasion, but the effect of SETD5 on NSCLC cell sternness characteristics is unknown. Thus we attempted to evaluate the effect of SETD5 on NSCLC sternness and its mechanism. Methods: The expressions of SETD5 and sternness-related genes (SOX2, OCT4, ABCG2) were detected in NSCLC tissues by immunohistochemistry assay, qRT-PCR, and western blot. A SETD5 knockdown cell model was constructed by siRNA transfection in A549 and H1299 cells. A CCK8 assay was used to examine cell viability. A sphere-forming assay and side population cell assay were conducted to measure the cancer cell stern properties. The cells with SETD5 deletion were treated with an activator of AKT, SC79, and the protein expressions of Akt, p-Akt, mTOR, and p-inTOR were assessed. Results: SETD5 and cancer stem-related genes SOX2, OCT4, and ABCG2 were co-expressed and co-localized in tumor tissues and cell lines of NSCLC. The deletion of SETD5 significantly reduced the cell viability, cancer stem properties, and activity of the PI3K/Akt/mTOR pathway, while the decreased SETD5-induced effects were partially restored with SC79 treatment. Conclusion: In this study, SETD5 promoted the cancer stem cell property of NSCLC through mitigating the activation of the PI3K/Akt/mTOR pathway, suggesting a candidate target role for SETD5 in NSCLC treatment.