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  • Title: LncRNA TTN-AS1 contributes to gastric cancer progression by acting as a competing endogenous RNA of miR-376b-3p.
    Author: Dong MM, Peng SJ, Yuan YN, Luo HP.
    Journal: Neoplasma; 2019 Jul 23; 66(4):564-575. PubMed ID: 30943745.
    Abstract:
    Long noncoding RNAs (lncRNAs) were reported to participate in the progression of gastric cancer (GC). However, litter 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.
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