Home HOME Neoplasma 2019 Neoplasma Vol.66, No.4, p.564-575, 2019

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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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Neoplasma Vol.66, No.4, p.564-575, 2019

Title: LncRNA TTN-AS1 contributes to gastric cancer progression by acting as a competing endogenous RNA of miR-376b-3p
Author: M. M. Dong, S. J. Peng, Y. N. Yuan, H. P. Luo

Abstract: Long noncoding RNAs (lncRNAs) were reported to participate in the progression of gastric cancer (GC). However, little is known about the biological functions of TTN antisense RNA 1 (TTN-AS1) in GC. Using qRT-PCR examination, we found that TTN-AS1 was expressed at a higher level in GC tissues and cell lines compared to the normal controls. Kaplan-Meier analysis of GC patients revealed the negative correlation between TTN-AS1 expression and the overall survival. To detect the biological function of TTN-AS1 in GC, we silenced TTN-AS1 to perform loss-of-function assays. The experimental results revealed that knockdown of TTN-AS1 obviously inhibited GC cell proliferation, induced cell apoptosis and impaired cell migration and invasion. In mechanism, TTN-AS1 was located in the cytoplasm of GC cells, indicating the post-transcriptional regulation of TTN-AS1 on gene expression. Bioinformatics analysis revealed the potential binding relation between TTN-AS1 and miR-376b-3p as well as between miR-376b-3p and KLF12. Mechanism experiments such as luciferase reporter assay and RNA pull-down assay demonstrated the interaction between TTN-AS1 and miR-376b-3p as well as between miR-376b-3p and KLF12 in GC cells. At last, rescue assays certified that miR-376b-3p and KLF12 involved in TTN-AS1-mediated GC progression. Similarly, the role of TTN-AS1-miR-376b-3p-KLF12 axis in GC progression was analyzed and validated. Taken together, we concluded that TTN-AS1 might function as a novel potential therapeutic target in the treatment of gastric cancer.

Keywords: TTN-AS1, miR-376b-3p, KLF12, gastric cancer, ceRNA
Published online: 29-Jul-2019
Year: 2019, Volume: 66, Issue: 4 Page From: 564, Page To: 575

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