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Inhibition of lncRNA PART1 Chemosensitizes Wild Type but Not KRAS Mutant NSCLC Cells

Authors Chen SC, Diao YZ, Zhao ZH, Li XL

Received 8 January 2020

Accepted for publication 14 April 2020

Published 10 June 2020 Volume 2020:12 Pages 4453—4460


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yong Teng

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 China

Correspondence: Xiao-Ling Li
Medical 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 China
Tel/Fax +86-24-31916361
Email [email protected]

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

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