LINC00894, YEATS2-AS1, and SUGP2 genes as novel biomarkers for N0 status of lung adenocarcinoma

Research on genes affecting tumors without lymph node metastasis is limited, hence this study employed both bioinformatic and experimental approaches to identify specific genes associated with lung cancer adenocarcinoma (LUAD) before lymph node metastasis occurs. Expression profiles of mRNAs and lncRNAs and LUAD clinical data were downloaded from the Cancer Genome Atlas (TCGA) using R software to identify differentially expressed genes (DEGs) associated with N0 and N + status. TargetScan, miRTarBase, and miRDB databases were used to identify interactions between miRNAs and mRNAs. The DIANA database and lncBase tool were used to find the association between lncRNA and miRNA. After selecting some genes, the expression of candidate genes was confirmed by real-time RT-PCR technique. Following the knockdown LINC00894 gene using the shRNA technique, its effect on invasion, migration, and apoptosis in the calu-3 cell line was investigated. In total, we found 321 specific DEGs not only in N0 vs. normal but also in N0 Vs. N + in LUAD, most of which were lncRNA and we identified a ceRNA network containing nine lncRNAs with the highest degree of connectivity. Among them, in addition to bioinformatic analyses, LINC00894 and YEATS2-AS1 were significantly increased in tumor tissues compared to normal tissues (P = 0.0001). also, SUGP2 that was shared in both lncRNA-related ceRNA subnetworks was significantly upregulated (P = 0.0001). Additionally, following the knockdown of LINC00894 in Calu-3 cell line, a significant decrease in migration and invasion was observed, but early apoptosis was significantly increased in the shLINC00894(48 h) group (P = 0.007). The findings of the present study show that lncRNAs play an important role in the N0 status of LUAD. Moreover, LINC00894, YEATS2-AS1, and SUGP2 can act as biomarkers in patients with N0 LUAD.