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

Xiaobo Guo,Yun Wang

doi:10.1002/cam4.3046

Abstract

PurposeHepatocellular 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.MethodsThe 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.ResultsTMPO‐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.ConclusionTMPO‐AS1 contributes to HCC progression by sponging miR‐329‐3p to activate FOXK1‐mediated AKT/mTOR signaling pathway.

Highlights

Hepatocellular carcinoma (HCC) is identified as one of the main reasons of caner-associated death in the world and half of death cases occur in China.[1,2] People have a high risk of developing HCC.[3,4] the oncological and surgical treatments have been improved in recent years, the prognosis of HCC patients is still not optimistic and the postoperative recurrence rate is high, resulting in that the survival rate of HCC patients is low.[1,2,5,6] It is well-known that the molecular mechanisms underlying the biological processes of HCC are not well-researched, which requires us to find a new long non-coding RNAs (lncRNAs) that may contribute to the diagnosis and prognosis of patients.LncRNAs are a subgroup of non-coding RNAs that have no or limited protein-coding ability, consisting of more than 200 nucleotides.[7]
Many papers have documented that lncRNAs play crucial roles in HCC progression
LncRNAs can serve as therapeutic targets for HCC patients

Summary

| INTRODUCTION

Hepatocellular carcinoma (HCC) is identified as one of the main reasons of caner-associated death in the world and half of death cases occur in China.[1,2] People have a high risk of developing HCC.[3,4] the oncological and surgical treatments have been improved in recent years, the prognosis of HCC patients is still not optimistic and the postoperative recurrence rate is high, resulting in that the survival rate of HCC patients is low.[1,2,5,6] It is well-known that the molecular mechanisms underlying the biological processes of HCC are not well-researched, which requires us to find a new lncRNA that may contribute to the diagnosis and prognosis of patients. The oncological and surgical treatments have been improved in recent years, the prognosis of HCC patients is still not optimistic and the postoperative recurrence rate is high, resulting in that the survival rate of HCC patients is low.[1,2,5,6]. It is well-known that the molecular mechanisms underlying the biological processes of HCC are not well-researched, which requires us to find a new lncRNA that may contribute to the diagnosis and prognosis of patients. Many studies show that lncRNAs play important roles in the biological development of cancer cells, such as cell proliferation, migration, and EMT formation.[10-12]. In this study, we will be exploring the biological function of TMPO-AS1in HCC progression, which might inspire us to find an effective treatment target for HCC

| MATERIALS AND METHODS

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Findings

| DISCUSSION