Cai Hui, Chen Jingde, He Bin, Li Qiang, Li Yandong, Gao Yong
Department of Oncology, East Hospital, Tongji University School of Medicine, 150 Ji-Mo Road, Shanghai, 200120, China.
Mol Cell Biochem. 2015 Aug;406(1-2):31-41. doi: 10.1007/s11010-015-2421-3. Epub 2015 Apr 24.
Long non-coding RNAs (LncRNAs) have been reported that play important roles in the progression and metastasis of some carcinomas. In the present study, we identified a new LncRNA, FRLnc1, from a microarray analysis in which those LncRNAs were regulated by FOXM1, an oncogene widely studied in most malignancies. Quantitative real-time PCR (qRT-PCR) results in gastric cancer cell lines indicated FRLnc1 expression is positively correlated with FOXM1 level, supporting the microarray data. Furthermore, the RNA level of FRLnc1 is upregulated in 49% (20/41) of cancer samples compared with neighboring non-cancerous stomach tissues. The in vitro functional analyses demonstrated that FRLnc1 knockdown by RNA interference suppressed cell migration in MGC803 and AGS cells, whereas FRLnc1 overexpression promoted cell migration in BGC823 and SGC7901 cells. Moreover, FRLnc1 could enhance the distant metastasis of SGC7901 cells by tail vein injection approach in mice. We also identified TGFβ1 and Twist as the downstream effectors of FRLnc1 in the regulation of cell migration by qRT-PCR analysis. Taken together, our findings suggest that FRLnc1 is involved in gastric cancer cell migration and for the first time set up the link between FOXM1 and LncRNA in cancer.
据报道,长链非编码RNA(LncRNAs)在某些癌症的进展和转移中发挥重要作用。在本研究中,我们通过微阵列分析鉴定了一种新的LncRNA,即FRLnc1,在该分析中,这些LncRNAs受FOXM1调控,FOXM1是一种在大多数恶性肿瘤中被广泛研究的癌基因。胃癌细胞系中的定量实时PCR(qRT-PCR)结果表明,FRLnc1表达与FOXM1水平呈正相关,这支持了微阵列数据。此外,与相邻的非癌性胃组织相比,49%(20/41)的癌症样本中FRLnc1的RNA水平上调。体外功能分析表明,通过RNA干扰敲低FRLnc1可抑制MGC803和AGS细胞的迁移,而FRLnc1过表达则促进BGC823和SGC7901细胞的迁移。此外,FRLnc1可通过尾静脉注射法增强SGC7901细胞在小鼠体内的远处转移。我们还通过qRT-PCR分析确定TGFβ1和Twist是FRLnc1在调节细胞迁移中的下游效应因子。综上所述,我们的研究结果表明FRLnc1参与胃癌细胞迁移,并首次在癌症中建立了FOXM1与LncRNA之间的联系。