Effects of the receptor-like protein tyrosine phosphatase PTPRH overexpression on gene expression in non-small cell lung cancer cell lines

The delicate balance of protein phosphorylation is often disrupted in cancers, with hyperactivity of kinases and inactivation of phosphatases driving cell proliferation and survival pathways. PTPRH, a receptor-like protein tyrosine, is deregulated or mutated in certain cancers, including non-small cell lung cancer (NSCLC). Nonetheless, the biological processes that PTPRH is involved in and how it may contribute to tumorigenesis are unknown. We aimed to understand how ovexpression of PTPRH affects tyrosine kinase signaling and in which biological processess this tyrosine phosphatase is involved in. We observed that overexpression of the phosphatase downregulates multiple oncogenic signature pathways and modulates the gene expression of 34 protein tyrosine phosphatases and 45 tyrosine kinases, EGFR included. Moreover, we report for the first time that PTPRH is primarily involved in translation and RNA-associated pathways. Together, these results shed light on the importance of PTPRH in regulating biological and cellular processes and how its inactivation may support cancer progression. To understand how PTPRH affects cell signaling pathways, we generated a NSCLC cell line PTPRH knockout (NCI-H23 PTPRH knockout) and stably overexpressed human PTPRH wild-type in two NSCLC cell lines (NCI-H23 PTPRH knockout and NCI-H2023). The parental cells expressing endogenous PTPRH were used as controls. Cells were serum starved for 24 hours, followed by FBS stimulation for 16 hours prior to collection of total RNA. Sequencing of the mRNA was performed in the Illumina platform (PE150) with a minimum coverage of 30M reads. We used n=3 technical replicates/group.