Chimeric RNA RRM2-C2orf48 plays an oncogenic role in the development of NNK-induced lung cancer

Chimeric RNAs have been used as biomarkers and therapeutic targets for multiple types of cancers. However, less attention has been paid to their mechanism of action in neoplasia. Here, we report that chimeric RNA RRM2-C2orf48 promotes 4-(methyl nitrosamine)-1-(3-pyridinyl)-1-butanone (NNK)-induced lung cancer. We found that RRM2-C2orf48 had higher expression levels in lung cancer cell lines and in lung cancer tissues from 74 patients than in normal cells and tissues, respectively. And its expression level was correlated with smoking. Next, we demonstrate that the expression level of RRM2-C2orf48 could increase after treatment with 200 mg/L NNK for 24 h. Overexpressing RRM2-C2orf48 accelerated the process of NNK-induced lung cancer and promoted cell growth. Meanwhile, suppressing RRM2-C2orf48 inhibited cell growth. Finally, we identified miR-219a-2-3p as a potential target of RRM2-C2orf48. In summary, RRM2-C2orf48 accelerated the process of NNK-induced lung cancer and miR-219a-2-3p may be involved in this process. Overall design: Comparative gene expression profiling of RNA-seq data from BEAS-2B cells and their NNK-induced malignant transformed cells (2B-NNK)