Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Currently, treatment methods generally cause poor prognosis. Therefore, in order to seek new treatment options, we explored the internal mechanism of NSCLC. Firstly, the SOX2-OT/miR-30d-5p/PDK1 axis regulated by lncRNA SOX2-OT was predicted by bioinformatics methods, and the expression of SOX2-OT, miR-30d-5p, and PDK1 mRNA in cells were detected by qRT-PCR while PDK1 protein expression was detected by western blot. The results expressed that in NSCLC, SOX2-OT, and PDK1 were notably overexpressed while miR-30d-5p was markedly under-expressed. The interaction between them was verified by dual-luciferase reporter and RNA binding protein immunoprecipitation assays. Subsequently, through CCK8, scratch healing, cell invasion and flow cytometry assays, we revealed that inhibiting the expression of SOX2-OT could inhibit the proliferation, migration and invasion of NSCLC cells and promote cell apoptosis; while simultaneous overexpression of PDK1 or inhibition of miR-30d-5p expression could reverse the inhibitory effect of SOX2-OT silence-mediated malignant progression of NSCLC cells. Then, the combined application of overexpressed PDK1 and rapamycin verified that PDK1 could regulate the expression of PD-L1 in NSCLC cells through the mTOR signaling pathway. Co-culture of CD8+ T cells verified that silencing SOX2-OT could inhibit the apoptosis of CD8+ T cells through miR-30d-5p/PDK1. Finally, tumor formation assay in animals confirmed that overexpression of SOX2-OT could promote the growth of NSCLC tumor in vivo. In this study, assays in vitro and in vivo were conducted to elucidate the mechanism by which SOX2-OT/miR-30d-5p/PDK1 drives PD-L1 through the mTOR signaling pathway to promote the malignant progression and immune escape of NSCLC.
Highlights
Lung cancer is the leading cause of cancer-related deaths globally, killing about 1,700,000 people each year
Analysis of SOX2-OT expression levels in different tissues revealed that SOX2-OT was notably highly expressed in Non-small cell lung cancer (NSCLC) tumor tissue (Figure 1B). qRT-PCR detection expressed that SOX2OT expression in NSCLC cell lines was remarkably higher than that of BEAS-2B cell line (Figure 1C), indicating that SOX2-OT had a potential cancer-promoting effect in NSCLC
In order to determine the role of SOX2-OT in the malignant progression of NSCLC, SOX2-OT was overexpressed in NCI-H460 cells which had relatively low expression of SOX2-OT, while SOX2-OT was silenced in A549 cells which had relatively high expression of SOX2-OT
Summary
Lung cancer is the leading cause of cancer-related deaths globally, killing about 1,700,000 people each year. For NSCLC patients, after initial diagnosis, corresponding treatment plan should be formulated according to the TNM stage. Surgical treatment is the main treatment for early or partial middle stage NSCLC patients, and chemotherapy alone or radiotherapy combined with chemotherapy is generally given to some middle and advanced NSCLC patients (Miller et al, 2016). Surgical treatment is the best cure, but most of the patients are in the advanced stage of NSCLC at the time of diagnosis and cannot be treated by surgery. In recent years, more and more doctors and scholars focus on targeted therapy. In-depth exploration of the internal molecular mechanism of NSCLC can provide new therapeutic targets for targeted therapy of NSCLC, and provide a theoretical basis for the study of prognostic biomarkers of NSCLC
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