ITGB1‐DT and ITGB1 enhance lung cancer cell metastatic abilities and are associated with poor prognoses in NSCLC patients

Non‐small cell lung cancer (NSCLC) is one of the major leaders in lethal cancer for decades. It has two major types: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In the molecular analysis, the genomic backgrounds were different among two sub‐types. But most deaths from these two types of NSCLC were due to the metastatic cells which present different molecular characteristics compared to the primary cells. The differences may provide a key for novel diagnosis and/or therapeutic strategy to treat NSCLC. Here in this study, we have found a long non‐coding RNA, ITGB1‐DT (RP11‐462L8.1) and its neighboring gene, ITGB1 were found associated with poor prognosis of overall survival and recurrence‐free survival analysis from TCGA lung cancer cohort in both LUAD and LUSC. We determined the expression levels with our own clinical cohort and confirmed the findings. We also found that the ITGB1‐DT RNA expression levels were correlated to the higher invasion and migration abilities in CL1‐5 lung cancer cells compared to lower invasion and migration ability parental CL1‐0 cells. It is also involved in epithelial‐mesenchymal‐transition in A549 after TGF‐beta treatment. ShRNA induced inhibition of the ITGB1‐DT gene expression was found to reduce the invasion and migration ability of the highly aggressive NSCLC cells with endogenous ITGB1‐DT overexpression. Knockdown of IGTB1‐D1 in lung cancer cells also significantly suppressed cancer cell invasions and metastases in in‐situ human lung cancer established NSG mouse model. The putative molecular mechanisms of ITGB1_DT and ITGB1 in promoting lung cancer cell metastasis were elucidated. Together, our results identified a new long non‐coding RNA ITGB1‐DT who may interact with its neighbor coding gene ITGB1 to promote lung cancer cell metastasis. Inhibition of ITGB1‐DT and ITGB1 expressions and interactions may provide a novel treatment strategy to combat lung cancer patients with metastasis.