BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer

Tao Hu, Yu-Run Lu

Long non-coding RNAs (lncRNAs) are increasingly implicated in the regulation of the progression of malignancy. To clarify the relations among BCYRN1 (brain cytoplasmic RNA 1, a long non-coding RNA), c-MYC and cell metastasis of non-small-cell lung cancer (NSCLC). Real-time PCR was used to measure expression of BCYRN1 in NSCLC. Knockdown and overexpression of c-MYC were respectively performed using shRNA and lentivirus to investigate its effect on BCYRN1 expression. BCYRN1 was respectively knockdown and overexpressed by siRNA and BCYRN1 mimics to investigate its role in regulating cell metastasis in vitro. ChIP (chromatin immunoprecipitation) assay was performed to confirm the binding of c-MYC to the promoter of BCYRN1. Expression levels of matrix metalloproteinases (MMP9 and MMP13) were determined using real-time PCR and Western blotting. BCYRN1 is upregulated and targeted by c-MYC in NSCLC, leading to the increase of cell motility and invasiveness. RNA interference and lentivirus infection showed a positive correlation between the expressions of c-MYC and BCYRN1. ChIP assay confirmed the binding of c-MYC to the promoter region of BCYRN1 gene. In-vitro cell metastasis experiments demonstrated that BCYRN1 was necessary in the c-MYC-regulated cell migration and invasion. The mRNA and protein expression levels of MMP9 and MMP13 descended with the decreasing BCYRN1 level and ascended with the upregulation of BCYRN1. These findings uncover a regulatory mechanism in NSCLC cells involving the metastasis-promoting lncRNA BCYRN1 that improves expressions of the key metastasis-supporting proteins MMP9 and MMP13.