Human Antigen R (HuR) Facilitates miR-19 Synthesis and Affects Cellular Kinetics in Papillary Thyroid Cancer

Area of Science:

• Molecular Biology
• Gene Expression Regulation
• Cancer Biology

Background:

• Pre-messenger RNA (mRNA) splicing is crucial for eukaryotic gene expression, involving the removal of introns and ligation of exons.
• Mutations in splice sites or spliceosome components are linked to diseases, including neurodegenerative disorders and cancers.
• HuR (Human antigen R) is an RNA-binding protein that binds to AU-rich elements, often in 3' untranslated regions of mRNAs, and has been observed associated with spliceosomes.

Purpose of the Study:

• To investigate the role of HuR in the splicing and processing of specific microRNAs (miRNAs) within the miR-17-92 cluster.
• To determine if HuR controls the expression of miR-18a and miR-19a, and consequently affects cellular phenotypes.
• To explore the potential link between HuR, miRNA biogenesis, and cancer development.

Main Methods:

• HuR overexpression was induced in BCPAP and HEK-293T cells, followed by miRNA expression analysis using quantitative polymerase chain reaction (qPCR).
• Phenotypic effects, including cell proliferation, migration, and invasion, were assessed using cell counting, trypan blue staining, transwell assays, and crystal violet staining.
• HuR was knocked down using small interfering RNA (siRNA) to analyze miRNA expression and cellular kinetics.

Main Results:

• HuR was found to be associated with miR-19a in both BCPAP and HEK-293T cells.
• Silencing HuR led to decreased expression of miR-17-5p and miR-19a in BCPAP cells.
• Overexpression of HuR resulted in increased cellular proliferation, migration, and invasion rates, which were partially reversed by antimiR-19a treatment, indicating HuR upregulates miR-19a, promoting cancer-associated cellular processes.

Conclusions:

• HuR plays a significant role in stimulating the expression of miR-19a and miR-19b.
• This HuR-mediated upregulation of miR-19a/b contributes to increased cell proliferation, migration, and invasion.
• The findings establish a connection between HuR, miRNA biogenesis, and cellular modifications that promote cancer development.