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The oncogenic role of Ladinin-1 (LAD1), an anchoring filament protein, is largely unknown. In this study, we conducted a series of studies on the oncogenic role of LAD1 in lung adenocarcinoma (LUAD). Firstly, we analyzed the aberrant expression of LAD1 in LUAD and its correlation with patient survival, tumor immune infiltration, and the activation of cancer signaling pathways. Furthermore, the relationship between LAD1 expression and K-Ras and EGF signaling activation, tumor cell proliferation, migration, and colony formation was studied by gene knockout/knockout methods. We found that LAD1 was frequently overexpressed in LUAD, and high LAD1 expression predicts a poor prognosis. LAD1 exhibits promoter hypomethylation in LUAD, which may contribute to its mRNA upregulation. Single-sample gene set enrichment analysis (ssGSEA) showed that acquired immunity was negatively correlated with LAD1 expression, which was verified by the downregulated GO terms of "Immunoglobulin receptor binding" and "Immunoglobulin complex circulating" in the LAD1 high-expression group through Gene Set Variation Analysis (GSVA). Notably, the Ras-dependent signature was the most activated signaling in the LAD1 high-expression group, and the phosphorylation of downstream effectors, such as ERK and c-jun, was strongly inhibited by LAD1 deficiency. Moreover, we demonstrated that LAD1 depletion significantly inhibited the proliferation, migration, and cell-cycle progression of LUAD cells and promoted sensitivity to Gefitinib, K-Ras inhibitor, and paclitaxel treatments. We also confirmed that LAD1 deficiency remarkably retarded tumor growth in the xenograft model. Conclusively, LAD1 is a critical prognostic biomarker for LUAD and has potential as an intervention target. [ABSTRACT FROM AUTHOR]

Abstract: MicroRNAs (miRNAs) as a species of small non coding single stranded RNA of about 21–25 nucleotides have important roles in the development of different cancers. In present study, we found that the expression of miR-25 was up-regulated in 60 esophageal squamous cell carcinoma (ESCC) tissues compared with matched adjacent non-cancer tissues. Moreover, we demonstrated that the up-regulation of miR-25 was significantly correlated with the status of lymph node metastasis and TNM (Tumor, Node and Metastasis) stage. Furthermore, over-expression of miR-25 markedly promoted migration and invasion of ESCC cells. On the contrary, down-regulation of miR-25 inhibited the migration and invasion of cells. E-cadherin(CDH1) is a very important tumor metastasis suppressor. We further identified that miR-25 directly targeted CDH1 3′-untranslated region (3′UTR) and repressed the expression of CDH1. These results, for the first time, demonstrate that miR-25 promotes ESCC cell migration and invasion by suppressing CDH1 expression. [Copyright &y& Elsevier]