Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis.

Background: The relationships between long noncoding RNA (lncRNAs) and tumors have currently become one of the focuses on cancer studies. Our previous studies found repulsive guidance molecule b (RGMB) was downregulated in lung cancer which is associated with poor prognosis and cancer metastasis.The present study investigated the regulation of RGMB expression by lncRNA RGMB-AS and its role in lung cancer progression. Methods: The expression of lncRNA RGMB-AS and RGMB were detected in 56 paired NSCLC tissues and adjacent normal tissues by qRT-PCR assay. The relations of lncRNA RGMB-AS and RGMB expression with clinicopathological factors of NSCLC patients were explored. The lncRNA RGMB-AS was downregulated and overexpressed in A549 and H1299 cells, and its role in lung cancer was further investigated in vitro and in vivo. Results: The results of qRT-PCR showed that lncRNA RGMB-AS expression was significantly downregulated in NSCLC tissues than in adjacent normal tissues (P &lt; 0.05). Correlation analysis indicated that the expression of lncRNA RGMB-AS and RGMB mRNA were positively correlated (P &lt; 0.05). The downregulation of lncRNA RGMB-AS in NSCLC tissues were associated with poor overall survival status(P &lt; 0.05). Downregulation of lncRNA RGMB-AS in A549 and H1299 cells subsequently results in reduced RGMB mRNA and protein expression. The downregulation/overexpression of lncRNA RGMB-AS significantly promoted/inhibited NSCLC cells metastasis in vitro and in vivo. Conclusion: We identified lncRNA RGMB-AS which was downregulated in NSCLC patients and thereby to reduce RGMB expression. lncRNA RGMB-AS might inhibit lung cancer metastasis via the regulation on RGMB and other tumor suppressors. Citation Format: Jin Li, Shi Xiaoshun, He Jianxing. A novel lncRNA RGMB-AS inhibit NSCLC metastasis via upregulating the expression of target gene RGMB. [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer: Mechanisms to Medicines ; 2015 Dec 4-7; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2016;76(6 Suppl):Abstract nr A08.