MLK3 is a newly identified microRNA-520b target that regulates liver cancer cell migration.

Fei Zhang,Dong Yang,Yu Zhu,Nianxiang Wu,Shuhua Wu,Lirun Qian,Guodong Hou,Irina V Lebedeva

doi:10.1371/journal.pone.0230716

Abstract

The roles of microRNAs (miRNAs) in liver cancer have attracted much attention in recent years. In this study, we demonstrate that miR-520b is downregulated in MHCC-97H cells, a liver cancer cell line with high potential of metastasis, compared with MHCC-97L cells which has a low potential of metastasis. Furthermore, the enhanced expression of miR-520b could inhibit liver cancer cell migration, while silencing its expression resulted in increased migration. Mixed lineage kinase 3 (MLK3) was identified as a direct and functional new target of miR-520b. This regulation was also confirmed by luciferase reporter assays. In addition, our results showed that overexpression of the MLK3 expression partially reversed the effect of miR-520b on liver cancer cell migration, indicating that MLK3 contributes to the migration in liver cancer. The newly identified miR-520b/MLK3 axis partially elucidates the molecular mechanism of liver cancer cell migration and represents a new potential therapeutic target for liver cancer treatment.

Highlights

Liver cancer is one of the most common malignancies and the second leading cause of cancer related death worldwide, in Southeast Asia, including China, Korea and Japan [1]
Our result showed that Mixed lineage kinase 3 (MLK3) overexpression increased the migration of MHCC-97L cells and MLK3 knockdown decreased the migration of MHCC-97H cells, which further confirmed the function of MLK3 in the regulation of liver cancer migration (Fig 4E)
We showed that silencing HBXIP or EGFR could inhibit the migration of HepG2 cells, which suggests that the other target genes of miR-520b contribute to the migration of liver cancer cells except MLK3

Summary

Introduction

Liver cancer is one of the most common malignancies and the second leading cause of cancer related death worldwide, in Southeast Asia, including China, Korea and Japan [1]. Generation sequencing of liver cancer patients has revealed that tons of genes are deregulated during the progression of liver cancer, and that the dysregulation of these genes are closely correlated with liver cancer diagnosis and prognosis [2, 3]. It is important to identify the dysregulated genes in liver cancer and to investigate their roles in liver cancer carcinogenesis and progression. MicroRNAs are a class of short noncoding RNAs, which are able to inhibit the expression of their target genes through binding with the 3’-untranslated region of target mRNA [4]. MiRNAs are closely involved in tumor development, such as tumor proliferation, migration or metastasis [5, 6].

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Discussion

Conclusion