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

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.

miRGediNET: A comprehensive examination of common genes in miRNA-Target interactions and disease associations: Insights from a grouping-scoring-modeling approach

“…Also, miRNA-520B was shown before to play different roles in different types of cancer, including colorectal, head and neck, liver, breast, and other cancers [ 51 ], [[ 52 ] p. 4], [ 53 , 54 ]. Our data confirm that our model can discover new genes important in tumor biology.…”

Phosphorylation of mixed lineage kinase MLK3 by cyclin-dependent kinases CDK1 and CDK2 controls ovarian cancer cell division

“…Furthermore, MLK3 regulates matrix metalloproteinases (MMPs), which are required for ovarian J o u r n a l P r e -p r o o f and breast cancer cell invasion (14,16). Moreover, MLK3 expression is targeted by microRNAs (miRNAs) to promote melanoma proliferation and invasion, and liver cancer cell migration (12,13).…”

“…Mixed lineage kinase 3 (MLK3) is a serine/threonine mitogen-activated protein kinase (MAPK) kinase kinase (MAP3K) ( 1 , 2 , 3 ) that is required for invasion and proliferation of ovarian cancer cells, and its activity and expression are higher in ovarian cancer cells than normal ovarian epithelial cells ( 4 , 5 , 6 ). In addition to ovarian cancer, MLK3 also plays an essential role in controlling cell proliferation, migration, invasion, and metastasis in other type of cancers, including triple-negative breast cancer, gastric cancer, liver cancer, colorectal cancer, and melanoma ( 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 ). In breast cancer cells, MLK3 regulates invasion and migration through c-Jun N-terminal kinase (JNK) signaling and paxillin phosphorylation to drive metastasis ( 7 , 8 ).…”

FGF16 regulated by miR-520b enhances the cell proliferation of lung cancer

“…GATA6/miR-520b/CREB1 is involved in gastric cancer [ 31 ]. MLK3, as a novel target gene of miR-520b, functions in liver cancer [ 32 ]. In non-small cell lung cancer miR-520b can repress the growth and migration via regulating CHAF1A [ 33 ].…”