Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Department of Medical Oncology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China.
Hebei University, Baoding, Hebei 071000, China.
Cell Biol Int. 2019 Apr;43(4):384-393. doi: 10.1002/cbin.11092. Epub 2019 Feb 6.
Non-small-cell carcinoma (NSCLC) is the most common cancer along with high mortality rate worldwide. In the present study, our data showed that lncRNA MAF BZIP Transcription Factor G Antisense RNA 1 (MAFG-AS1) was over-expressed in NSCLC tissues and cell lines. Overexpression of MAFG-AS1 promoted the migration, invasion and enhanced epithelial-mesenchymal transition (EMT) of NSCLC cell. In addition, miR-339-5p was predicted to be a target of MAFG-AS1 and the level of miR-339-5p was down-regulated in NSCLC. Over-expression of MAFG-AS1 significantly decreased the level of miR-339-5p in NSCLC cell. Moreover, the matrix metalloproteinase 15 (MMP15) was identified to be a target of miR-339-5p. The level of MMP15 was negatively regulated by miR-339-5p whereas positively controlled by MAFG-AS1. In addition, up-regulation of miR-339-5p neutralized the promoting impact of MAFG-AS1 on the migration, invasion and EMT of NSCLC cell. Finally, the xenograft model suggested that MAFG-AS1 promoted the metastasis of NSCLC cell in vivo. Altogether, we proved that MAFG-AS1-miR-339-5p-MMP15 axis might be a promising therapeutic target for the treatment of patients with NSCLC.
非小细胞癌 (NSCLC) 是全球最常见的癌症之一,死亡率也很高。在本研究中,我们的数据显示,lncRNA MAF BZIP 转录因子 G 反义 RNA 1 (MAFG-AS1) 在 NSCLC 组织和细胞系中表达上调。MAFG-AS1 的过表达促进了 NSCLC 细胞的迁移、侵袭和上皮间质转化 (EMT)。此外,miR-339-5p 被预测为 MAFG-AS1 的靶点,并且在 NSCLC 中 miR-339-5p 的水平下调。MAFG-AS1 的过表达显著降低了 NSCLC 细胞中 miR-339-5p 的水平。此外,基质金属蛋白酶 15 (MMP15) 被鉴定为 miR-339-5p 的靶点。MMP15 的水平受 miR-339-5p 的负调控,而受 MAFG-AS1 的正调控。此外,miR-339-5p 的上调中和了 MAFG-AS1 对 NSCLC 细胞迁移、侵袭和 EMT 的促进作用。最后,异种移植模型表明,MAFG-AS1 促进了 NSCLC 细胞在体内的转移。总之,我们证明了 MAFG-AS1-miR-339-5p-MMP15 轴可能是治疗 NSCLC 患者的有前途的治疗靶点。