Anhui Vocational College of Defense Technology, Lu'an, Anhui, China.
The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
PLoS One. 2020 Mar 26;15(3):e0230716. doi: 10.1371/journal.pone.0230716. eCollection 2020.
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.
近年来，微小 RNA（miRNA）在肝癌中的作用引起了广泛关注。在这项研究中，我们证明与具有低转移潜能的 MHCC-97L 细胞相比，高转移潜能的肝癌细胞系 MHCC-97H 中 miR-520b 的表达下调。此外，miR-520b 的增强表达可抑制肝癌细胞迁移，而沉默其表达则导致迁移增加。混合谱系激酶 3（MLK3）被鉴定为 miR-520b 的一个直接和功能新靶标。这一调控也通过荧光素酶报告基因检测得到了证实。此外，我们的结果表明，MLK3 表达的过表达部分逆转了 miR-520b 对肝癌细胞迁移的影响，表明 MLK3 有助于肝癌的迁移。新鉴定的 miR-520b/MLK3 轴部分阐明了肝癌细胞迁移的分子机制，代表了肝癌治疗的新的潜在治疗靶点。
