OncoTargets and Therapy (Jun 2020)
Upregulated lncRNA CASC9 Contributes to Progression of Non-Small Cell Lung Cancer Through Inhibition of miR-335-3p and Activation S100A14 Expression
Abstract
Weigang Zhao,1,* Tangbing Chen,2,* Yonghong Zhao1 1Department of Thoracic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200030, People’s Republic of China; 2Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yonghong ZhaoDepartment of Thoracic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishanlu Road, Xuhui District, Shanghai 200030, People’s Republic of ChinaEmail [email protected]: Non-small cell lung cancer (NSCLC) is a deadly cancer type worldwide and the main sub-type of lung cancer. Cancer susceptibility candidate-9 (CASC9) was reported to be a key player in cancer progression. However, its function and underlying mechanism in NSCLC remain unclear.Materials and Methods: Expression level of CASC9 in NSCLC tissues and cells was measured with RT-qPCR. Biological roles of CASC9 in NSCLC were analyzed with a series of in vitro experiments. Potential mechanisms of CASC9 in NSCLC were analyzed by predicting and validating the possible targets of CASC9 in NSCLC.Results: In this study, we found CASC9 expression was upregulated in NSCLC tissues and cell lines. High CASC9 expression was identified as a predictor for poorer overall survival of NSCLC patients. Furthermore, functional assays showed CASC9 knockdown suppressed NSCLC cell proliferation, migration, and invasion, while CASC9 overexpression caused opposite effects. We also found microRNA-335-3p (miR-335-3p) could act as a target of CASC9 in NSCLC and the inhibition effect of CASC9 knockdown on NSCLC progression required the activity of miR-335-3p. In addition, we identified S100 calcium-binding protein A14 (S100A14) acts as a target of miR-335-3p.Discussion: Taken together, our study suggested CASC9 could promote NSCLC progression via miR-335-3p/S100A14 axis. The CASC9/miR-335-3p/S100A14 regulatory triplets identified in this work might provide new therapeutic strategies for NSCLC treatment.Keywords: non-small cell lung cancer, CASC9, miR-335-3p, S100A14, ceRNA
