Sun Yonghong, Han Chunyao
Department of General Surgery, Second Hospital of Shanxi Medical University, Taiyuan City, Shanxi Province 030001, People's Republic of China.
Cancer Manag Res. 2020 Feb 20;12:1261-1268. doi: 10.2147/CMAR.S235898. eCollection 2020.
Mounting evidence show that long non-coding RNAs (lncRNAs) play critical roles in the progression of various human cancers, including gastric cancer (GC), a common gastrointestinal tumor. In this study, the biological functions of lncRNA TMPO-AS1 in GC were studied.
TMPO-AS1 and miR-140-5p expression levels were detected in GC tissues and cell lines by RT-qPCR analysis. Knockdown or overexpression of TMPO-AS1 was conducted to evaluate the effects of TMPO-AS1 on the malignant behaviors of GC cells. Bioinformatic prediction and dual-luciferase reporter assay were performed to investigate the direct interaction between TMPO-AS1 and miR-140-5p in GC.
We observed that TMPO-AS1 was up-regulated in GC tissues, and high TMPO-AS1 expression in GC patients was closely correlated with aggressive clinicopathologic characteristics and poor overall survival. Functionally, gain- and loss-of-function studies showed that TMPO-AS1 overexpression enhanced the proliferation, migration, invasion and EMT of GC cells in vitro, whereas knockdown of TMPO-AS1 inhibited these malignant traits. Importantly, we demonstrated that TMPO-AS1 could function as a competing endogenous RNA (ceRNA) by sponging miR-140-5p in GC cells, thereby diminishing the inhibition on SOX4, an EMT regulator.
Our findings indicated that TMPO-AS1 promotes GC progression partly by regulating miR-140-5p/SOX4 axis, and may serve as a novel therapeutic target for GC.
越来越多的证据表明,长链非编码RNA(lncRNA)在包括胃癌(GC)这种常见胃肠道肿瘤在内的多种人类癌症进展中发挥关键作用。在本研究中,我们对lncRNA TMPO-AS1在胃癌中的生物学功能进行了研究。
通过RT-qPCR分析检测胃癌组织和细胞系中TMPO-AS1和miR-140-5p的表达水平。进行TMPO-AS1的敲低或过表达以评估TMPO-AS1对胃癌细胞恶性行为的影响。进行生物信息学预测和双荧光素酶报告基因检测以研究胃癌中TMPO-AS1与miR-140-5p之间的直接相互作用。
我们观察到TMPO-AS1在胃癌组织中上调,胃癌患者中TMPO-AS1的高表达与侵袭性临床病理特征和较差的总生存期密切相关。在功能上,功能获得和功能丧失研究表明,TMPO-AS1过表达增强了胃癌细胞在体外的增殖、迁移、侵袭和上皮-间质转化,而TMPO-AS1的敲低则抑制了这些恶性特征。重要的是,我们证明TMPO-AS1在胃癌细胞中可通过海绵吸附miR-140-5p发挥竞争性内源RNA(ceRNA)的作用,从而减弱对EMT调节因子SOX4的抑制。
我们的研究结果表明,TMPO-AS1部分通过调节miR-140-5p/SOX4轴促进胃癌进展,可能成为胃癌的一个新的治疗靶点。