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Y-Box Binding Protein 1: A Potential New Target for Cancer Treatment

A study by researchers from the Dalian Institute of Chemical Physics of the Chinese Academy of Sciences have uncovered the underlying mechanism of how Y-box binding protein 1 promotes cancer metastasis.

Cancer is the uncontrolled division of cells in our bodies. When they spread from one part of the body to another, they are said to have metastasised. Metastasis of cancer is the main cause of cancer-related death and remains a challenge of cancer treatment.

The Y-box binding protein 1 (YB1 or YBX1) is a nucleotide-binding protein that plays an important role in tumorigenesis and cancer progression. However, whether YB1 affects malignant transformation by modulating non-coding RNAs remains largely unknown. In this study, researchers led by Prof Piao Hailong from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) looked into the relationship between YB1 and microRNAs and found that YB1 promotes the metastasis of liver cancer by regulating the biosynthesis of microRNA.

MicroRNAs are small single-stranded non-coding RNA molecules involved in RNA silencing and post-transcriptional regulation of gene expression. To understand how the microRNA-mediated regulatory network can impact tumour malignancy, the researchers first screened microRNA dysregulation by YB1 through microarray analysis in liver cancer cells. The regulation of YB1 on microRNAs miR-205 and miR-200b was determined by quantitative real-time PCR, a dual-luciferase reporter assay, RNA immunoprecipitation, and a pull-down assay. Other relationships of YB1 with various proteins involved in microRNA biogenesis like DgCR8, Dicer, and TUT4 were identified by pull-down and co-immunoprecipitation experiments.

Researchers also explored YB1’s effect on tumour metastasis in mice models, and the expression levels of epithelial to mesenchymal transition markers were detected by immunoblotting and immunohistochemistry assays.

From their results, the team found that YB1 interacts with the different proteins involved in microRNA biosynthesis to significantly inhibit the synthesis and expression of microRNAs miR-205 and miR-200b. This downregulation of miR-205 and miR-200b enhances the expression of a key protein in cancer metastasis called ZEB1, leading to increased cell migration and invasion.

Prof Piao and colleagues’ work reveals a previously undescribed mechanism by which a nucleotide-binding protein YB1 promotes cancer progression by regulating microRNA miR-205/200b and ZEB1 interaction in liver cancer cells. These results suggest that YB1 may play a biological role in human cancers via microRNA-mediated gene regulation, thereby presenting us with a potential therapeutic target for future cancer treatment. [APBN]

Source: Piao et al. (2021). YB1 regulates miR-205/200b-ZEB1 axis by inhibiting microRNA maturation in hepatocellular carcinoma. Cancer Communications.