Department of Urology, Jiaxing Second Hospital, No.1518 North Ring Road, Jiaxing City, 314000, Zhejiang Province, People's Republic of China.
Hum Cell. 2021 Mar;34(2):588-597. doi: 10.1007/s13577-020-00470-3. Epub 2021 Jan 5.
MAFG-AS1 is an oncogenic lncRNA in multiple types of cancer. However, its role in bladder cancer (BC) remains unclear. The present study aimed to investigate the function of MAFG-AS1 in BC. BC and paired non-tumor tissues were collected. Two BC cell lines HT01197 and HT-1376 were used. Dual luciferase activity assay, RT-qPCR, western blot, CCK-8, transwell invasion assay, and wound healing assay were performed. We found that MAFG-AS1 was significantly up-regulated in BC tissues and predicted a poor survival rate. MAFG-AS1 interacted with miR-125b-5p. However, the expression levels of MAFG‑AS1 and miR-125b-5p were not obviously correlated in BC tissues, and MAFG‑AS1 and miR-125b-5p did not regulate the expression of each other. Interestingly, we found that SphK1, a downstream target of miR-125b-5p, was negatively correlated with miR-125b-5p, while it was positively correlated with MAFG-AS1 across BC tissues. In addition, overexpression of MAFG‑AS1 upregulated the expression of SphK1 in BC cells, and attenuated the inhibitory effects of miR-125b-5p on the expression of SphK1. Functional assays showed that overexpression of MAFG‑AS1 promoted BC cell proliferation, migration, and invasion, while its effects were attenuated by overexpression of miR-125b-5p. Moreover, overexpression of miR-125b-5p inhibited BC cell proliferation, migration, and invasion, while its effects were alleviated by overexpression of SphK1. Taken together, our findings demonstrated that MAFG-AS1 has an oncogenic role in BC by regulating the miR-125b-5p/SphK1 axis. MAFG-AS1 might serve as a good diagnostic marker and a potential therapeutic target of BC.
MAFG-AS1 是多种类型癌症中的致癌 lncRNA。然而，其在膀胱癌（BC）中的作用尚不清楚。本研究旨在探讨 MAFG-AS1 在 BC 中的功能。收集 BC 组织和配对非肿瘤组织。使用两种 BC 细胞系 HT01197 和 HT-1376。进行双荧光素酶活性测定、RT-qPCR、western blot、CCK-8、Transwell 侵袭实验和划痕愈合实验。我们发现 MAFG-AS1 在 BC 组织中显著上调，并预测生存率较差。MAFG-AS1 与 miR-125b-5p 相互作用。然而，BC 组织中 MAFG-AS1 和 miR-125b-5p 的表达水平没有明显相关，并且 MAFG-AS1 和 miR-125b-5p 彼此不调节表达。有趣的是，我们发现 SphK1，miR-125b-5p 的下游靶标，与 miR-125b-5p 呈负相关，而与 across BC 组织中的 MAFG-AS1 呈正相关。此外，MAFG-AS1 的过表达上调了 BC 细胞中 SphK1 的表达，减弱了 miR-125b-5p 对 SphK1 表达的抑制作用。功能测定表明，MAFG-AS1 的过表达促进了 BC 细胞的增殖、迁移和侵袭，而过表达 miR-125b-5p 则减弱了其作用。此外，miR-125b-5p 的过表达抑制了 BC 细胞的增殖、迁移和侵袭，而过表达 SphK1 则减轻了其作用。总之，我们的研究结果表明，MAFG-AS1 通过调节 miR-125b-5p/SphK1 轴在 BC 中发挥致癌作用。MAFG-AS1 可能作为 BC 的良好诊断标志物和潜在治疗靶点。
