Cancer Management and Research (Jun 2020)
Inhibition of lncRNA PART1 Chemosensitizes Wild Type but Not KRAS Mutant NSCLC Cells
Abstract
Shu-Chen Chen,1 Yu-Zhu Diao,1 Zi-Han Zhao,2 Xiao-Ling Li1 1Medical Oncology Department of Thoracic Cancer 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, Shenyang, Liaoning 110042, People’s Republic of China; 2The Second Clinical College of Dalian Medical University, Dalian, Liaoning 116044, People’s Republic of ChinaCorrespondence: Xiao-Ling LiMedical Oncology Department of Thoracic Cancer 1, Cancer Hospital of China Medical University, Liaoning Cancer Hospital, No. 44, Xiaoheyan Road, Dadong District, Shenyang, Liaoning 110042, People’s Republic of ChinaTel/Fax +86-24-31916361Email [email protected]: 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
