Cancer Management and Research (Dec 2020)
Long Noncoding RNA LINC01426 Sequesters microRNA-519d-5p to Promote Non-Small Cell Lung Cancer Progression by Increasing ETS1 Expression
Abstract
Jixin Dai,1 Bing Wang,2 Yueming Zhao,1 Xuerong Zuo,1 Hongxia Cui,1 Xi Chen,2 Xianhong Liu1 1Department of Oncology, Jilin Cancer Hospital, Changchun, Jilin 130000, People’s Republic of China; 2Department of Radiotherapy, Jilin Cancer Hospital, Changchun, Jilin 130000, People’s Republic of ChinaCorrespondence: Xianhong LiuDepartment of Oncology, Jilin Cancer Hospital, 1018 Huguang Road, Changchun, Jilin 130000, People’s Republic of ChinaEmail [email protected]: Recent studies have identified important roles for long intergenic non-protein coding RNA 1426 (LINC01426) in glioma and clear cell renal cell carcinoma. The present study evaluated the expression profile of LINC01426 in non-small cell lung cancer (NSCLC) tissues and cell lines. Furthermore, the function of LINC01426 in NSCLC and the molecular mechanisms involved were extensively studied.Methods: The abundance of LINC01426 in NSCLC tissues and cell lines was determined using quantitative reverse transcription–polymerase chain reaction. The cell counting kit-8 assay, flow cytometry, transwell experiments for migration and invasion, and xenograft tumor model were used to assess the function of LINC01426 in NSCLC cells. Mechanistic studies were performed using the luciferase reporter assay and RNA immunoprecipitation.Results: Significant LINC01426 upregulation was observed in NSCLC tissues and cell lines. Silencing LINC01426 inhibited proliferation, migration, and invasion of NSCLC cells and facilitated cell apoptosis in vitro. Furthermore, interference of LINC01426 restricted tumor growth of NSCLC cells in vivo. In addition, LINC01426 showed the ability to directly bind to microRNA-519d-5p (miR-519d-5p) and act as a molecular sponge for miR-519d-5p in NSCLC cells. Furthermore, the ETS proto-oncogene 1 (ETS1) was identified as a direct target of miR-519d-5p and LINC01426 could indirectly upregulate ETS1 expression by sponging miR-519d-5p. Moreover, the cancer-inhibiting activities of LINC01426 knockdown in NSCLC cells were partially offset by miR-519d-5p inhibition.Conclusion: LINC01426 increases ETS1 expression by sequestering miR-519d-5p, thereby aggravating the malignant progression of NSCLC. The LINC01426/miR-519d-5p/ETS1 competing endogenous RNA pathway may provide a target for designing therapeutic agents for NSCLC treatment.Keywords: long intergenic non-protein coding RNA 1426, NSCLC, ETS proto-oncogene 1, ceRNA
