Background: Lung cancer has the highest incidence among solid tumors in men and is the third most common cancer in women. Despite improved understanding of genomic and mutational landscape in non-small cell lung cancer (NSCLC), the five-year survival in these patients has remained stagnant at a dismal 15%. The first line of treatment commonly adapted for NSCLC patients with somatic mutation in EGFR  is tyrosine kinase inhibitor gefitinib or erlotinib. EGFR  mutant cells seem to be intrinsically sensitive to tyrosine kinase inhibitors; however, the remaining 20– 30% patients are resistant to tyrosine kinase inhibitor.
Materials and Methods: Here we show, using in vitro normal and NSCLS cell lines, that the lncRNA Prostate androgen-regulated transcript 1 (PART1 ) is expressed at higher levels in NSCLC cells compared to normal lung epithelial cell line, corroborating two earlier studies.
Results: We additionally show that these cells are resistant to erlotinib which is reversed in some, but not all, cell lines following suppression of PART1  expression. The differential response to erlotinib following siRNA-mediated knockdown of PART1  was found to be related to the mutational status of KRAS . Only in cells with wild-type KRAS  suppression of PART1  sensitized them to erlotinib. Knockdown of mutant KRAS  did not sensitize those cell lines to erlotinib. But knockdown of mutant KRAS  along with suppression of PART1  sensitized the cells to treatment with erlotinib. The results from the study reveal a yet undefined and important role of lncRNA PART1  in defining sensitivity to erlotinib. This action is mediated by mutation status of KRAS .
Conclusion: Even though preliminary, our results indicate PART1  might be a potential candidate for targeted therapy or used as a predictor of chemosensitivity in patients with NSCLC.
Keywords: lncRNA, PART1, KRAS, non-small cell lung cancer, chemosensitivity, erlotinib