Big data analytics for MerTK genomics reveals its double-edged sword functions in human diseases

Area of Science:

• Biochemistry
• Molecular Biology
• Genomics

Background:

• The MER proto-oncogene tyrosine kinase (MerTK) is a receptor tyrosine kinase involved in efferocytosis and redox-related human diseases.
• Understanding MerTK's role in various human cells, tissues, and disease states is crucial for therapeutic development.

Purpose of the Study:

• To explore the biology of MerTK in human cells, tissues, and diseases using big data analytics.
• To identify potential therapeutic strategies targeting MerTK based on its expression patterns and disease-specific alterations.

Main Methods:

• Analysis of human RNA-seq and scRNA-seq data from 42,700 samples obtained from NCBI Gene Expression Omnibus.
• Utilized QIAGEN Ingenuity Pathway Analysis (IPA) for comprehensive data analysis, including approximately 170,000 crossover analyses.
• Quantified MerTK expression using Log2 (FPKM + 0.1).

Main Results:

• MerTK is highly expressed in immune cells (macrophages, monocytes, T cells, B cells), progenitor cells, and endothelial cells (ECs).
• Elevated MerTK expression was observed in human tissues including plaque, blood vessels, heart, liver, CNS, and connective tissue.
• MerTK expression is altered in cardiovascular diseases, cancer, and brain disorders, with notable sex differences.

Conclusions:

• MerTK represents a promising therapeutic target, with modulation strategies dependent on disease type and sex.
• MerTK inhibition may be beneficial for cancer therapy by enhancing anti-tumor immunity.
• MerTK restoration shows potential for treating atherosclerosis and myocardial infarction due to its cleavage in these conditions.