LncRNA TMPO‐AS1 promotes hepatocellular carcinoma cell proliferation, migration and invasion through sponging miR‐329‐3p to stimulate FOXK1‐mediated AKT/mTOR signaling pathway

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.