Investigating the expression and role of the lncRNA EGFR-AS1 in lung cancer (360G-Wellcome-207286_Z_17_Z)

Targeted therapies, have led to significant improvements in our ability to treat non-small cell lung cancer (NSCLC). One of these targets is the EGFR receptor which if mutated at particular residues makes this receptor amenable to targeted therapies such as EGFR Tyrosine Kinase inhibitors (TKIs). Whilst this improves survival, at some point all patients will develop resistance to the existing therapies. long non-coding RNAs (lncRNAs), are known to play critical roles in resistance to chemotherapy and epithelial mesenchymal transition (EMT). One lncRNA, called EGFR-AS1 exists in an antisense orientation to the EGFR. The only study on this lncRNA is in hepatocellular carcinoma, where its expression was shown to be significantly related to patient prognosis, and its inhibition resulted in significantly reduced cellular proliferation and invasion in vivo. Nothing is known about the role of this lncRNA in NSCLC. Preliminary data from the PIs laboratory indicates that the expression of this lncRNA is significantly altered in cells carrying mutations which render them sensitive to EGFR TKIs. This aim of this project is to evaluate this possibility in NSCLC, and to test whether overexpression of this lncRNA increases sensitivity to EGFR TKIs in resistant cells and its effects on markers of EMT.