Identification of long non-coding RNAs associated with aberrant LKB1 signaling. Homo sapiens

The LKB1 tumor suppressor gene is frequently mutated and inactivated in many cancers, particularly non-small cell lung carcinoma (NSCLC). LncRNAs are a novel class of gene regulators with newly discovered roles in cancer development and progression. LncRNA involvement in altered LKB1 signaling in lung cancer is currently unknown. To investigate whether lncRNAs contribute to loss of LKB1 tumor suppression in lung tumorigenesis and maintenance, we performed genome-wide lncRNA transcriptional profiling to identify lncRNAs associated with aberrant LKB1 signaling. Overall design: We had 2 sets of experiments. (A) We compared lncRNA expression profiles in 2 groups of lung cancer cell lines, LKB1-null and LKB1-wt, and identified lncRNAs associated with loss of LKB1. LKB1-null (A549, H460) and LKB1-wt (H322, H3123) cells were harvested for isolation of RNA for microarray analysis. (B) We compared lncRNA expression profiles in three groups of cells by transducing LKB1-null A549 NSCLC cells with pBabe-based retroviruses harboring wild-type (wt) LKB1, LKB1 kinase-dead mutant (K78I), or vector control (Ctl). We then identified lncRNAs differentially regulated by LKB1-wt, or LKB1-K78I as compared with vector control cells. Two biological replicates for each sample group were prepared.