Long Non-Coding RNA TMPO-AS1 Promotes Cell Migration and Invasion by Sponging miR-140-5p and Inducing SOX4-Mediated EMT in Gastric Cancer

长链非编码RNA TMPO-AS1通过海绵吸附miR-140-5p并诱导SOX4介导的EMT,促进胃癌细胞的迁移和侵袭。

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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