Department of Gastrointestinal Surgery, Jiaxing First Hospital, Jiaxing, Zhejiang Province, P.R. China.
Oncol Res. 2018 Dec 27;27(1):65-71. doi: 10.3727/096504018X15191223015016. Epub 2018 Feb 22.
MicroRNAs (miRNAs) have been demonstrated to be essential regulators in the development and progression of various cancers. The role of miR-188-5p in gastric cancer (GC) has not been determined. In this study, we found that the expression of miR-188-5p was downregulated in GC tissues compared with adjacent normal tissues. The lowly expressed miR-188-5p was significantly associated with lymph node metastasis and advanced TNM stage. Moreover, overexpression of miR-188-5p significantly inhibited GC cell proliferation, migration, and invasion but promoted cellular apoptosis. Mechanistically, we identified transcription factor ZFP91 as a target gene of miR-188-5p in GC. We found that miR-188-5p overexpression significantly inhibited the expression of ZFP91 in GC cell lines. There was an inverse correlation between the expression of miR-188-5p and ZFP91 in GC tissues. We found that restoration of ZFP91 in miR-188-5p-overexpressed MGC-803 and SGC-7901 cells promoted cell proliferation, migration, and invasion. Finally, we also showed that overexpression of miR-188-5p inhibited tumor growth in vivo. Taken together, our findings indicated that miR-188-5p serves as a tumor suppressor in human GC by targeting ZFP91, suggesting that miR-188-5p might be a promising therapeutic target for GC treatment.
微小 RNA(miRNAs)已被证明是各种癌症发生和发展的重要调节因子。miR-188-5p 在胃癌(GC)中的作用尚未确定。在本研究中,我们发现 miR-188-5p 在 GC 组织中的表达低于相邻正常组织。低表达的 miR-188-5p 与淋巴结转移和晚期 TNM 分期显著相关。此外,miR-188-5p 的过表达显著抑制 GC 细胞的增殖、迁移和侵袭,但促进细胞凋亡。机制上,我们鉴定出转录因子 ZFP91 是 GC 中 miR-188-5p 的靶基因。我们发现 miR-188-5p 的过表达显著抑制 GC 细胞系中 ZFP91 的表达。GC 组织中 miR-188-5p 和 ZFP91 的表达呈负相关。我们发现,在 miR-188-5p 过表达的 MGC-803 和 SGC-7901 细胞中恢复 ZFP91 的表达促进了细胞的增殖、迁移和侵袭。最后,我们还表明 miR-188-5p 的过表达在体内抑制了肿瘤的生长。总之,我们的研究结果表明,miR-188-5p 通过靶向 ZFP91 作为人类 GC 的肿瘤抑制因子发挥作用,表明 miR-188-5p 可能成为 GC 治疗的有前途的治疗靶点。