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  • Title: LncRNA TMPO-AS1 promotes hepatocellular carcinoma cell proliferation, migration and invasion through sponging miR-329-3p to stimulate FOXK1-mediated AKT/mTOR signaling pathway.
    Author: Guo X, Wang Y.
    Journal: Cancer Med; 2020 Jul; 9(14):5235-5246. PubMed ID: 32462698.
    Abstract:
    PURPOSE: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Numerous analyses have revealed the abnormal expression of long non-coding RNAs (lncRNAs) in HCC cells. This study aims to explore biological functions of lncRNA TMPO-AS1 (TMPO antisense RNA 1) in HCC cell proliferation, apoptosis, invasion and migration. METHODS: The gene expression in HCC tissues and cell lines were measured by qRT-PCR. The role of TMPO-AS1 in HCC was confirmed by CCK-8, colony formation, TUNEL, transwell and western blot as well as by in vivo experiments. RNA pull down and luciferase reporter assays were utilized to prove the binding relationship between TMPO-AS1/FOXK1 (forkhead box K1) andmiR-329-3p. Rescue assays elucidated the regulatory effects of TMPO-AS1/miR-329-3p/FOXK1/AKT/mTOR pathway on cellular activities in HCC. RESULTS: TMPO-AS1was upregulated in HCC tissues and cells and its depletion inhibits HCC cell proliferation, invasion, migration, and EMT process as well as tumor growth. Furthermore, TMPO-AS1 could bind with miR-329-3p, which suppressed HCC cell proliferation. FOXK1 served as the target gene of miR-329-3p and TMPO-AS1 upregulated FOXK1 by sponging miR-329-3p in HCC cells. Additionally, FOXK1 overexpression or miR-329-3p inhibitor neutralized the repressing effects of TMPO-AS1 knockdown on HCC development. Finally, it verified that TMPO-AS1 could regulate AKT/mTOR pathway via FOXK1 to promote HCC. CONCLUSION: TMPO-AS1 contributes to HCC progression by sponging miR-329-3p to activate FOXK1-mediated AKT/mTOR signaling pathway.
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