Liang Gao,1,2 Xiaochen Chen,1,2 Yongxiang Wang,3 Jianbin Zhang1,2 1Department of Oncology, Zhejiang Provincial People’s Hospital, Hangzhou 310022, Zhejiang Province, People’s Republic of China; 2Department of Oncology, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, People’s Republic of China; 3Department of Abdominal Surgery, Zhejiang Cancer Hospital, Hangzhou 310022, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xiaochen ChenDepartment of Oncology, Zhejiang Provincial People’s Hospital, Hangzhou 310022, People’s Republic of ChinaTel +86 57185893183Email 3636636925@163.comBackground: Follistatin-like 3 (FSTL3) binds and inactivates activin, a growth factor with cell growth and differentiation. Previous studies reported that it is overexpressed in invasive breast cancers, and its expression and function in non-small cell lung cancer (NSCLC) remain unclear.Materials and Methods: Immunohistochemistry was employed to probe the expression of FSTL3 in NSCLC tissues. Real-time PCR (RT-PCR) was applied to detect the expression of lncRNA DSCAM-AS1 and miR-122-5p. A549 cells and H1299 cells were used as cell models. The biological influence of FSTL3 on cells was studied using CCK-8 assay, wound healing assay and transwell assay in vitro, respectively. In vivo subcutaneous xenotransplanted tumor model and tail vein injection model in mice were also constructed to validate the roles of FSTL3. Interactions between miR-122-5p and FSTL3, DSCAM-AS1 and miR-122-5p were determined by bioinformatics analysis, RT-PCR, and dual-luciferase reporter assay.Results: FSTL3 and DSCAM-AS1 were remarkably up-regulated in NSCLC samples, and miR-122-5p was down-regulated. FSTL3 was associated with worse prognosis of NSCLC patients. FSTL3 knockdown markedly inhibited the viability, migration and invasion of NSCLCs in vitro and in vivo. DSCAM-AS1 could down-regulate miR-122-5p via sponging it, and FSTL3 was a target gene of miR-122-5p.Conclusion: Taken together, our study identified that FSTL3 was a new oncogene of NSCLC, which was regulated by DSCAM-AS1 and miR-122-5p. These findings suggested that FSTL3, DSCAM-AS1 and miR-122-5p might serve as a new valuable therapeutic target for NSCLC.Keywords: FSTL3, NSCLC, lncRNA DSCAM-AS1, miR-122-5p, proliferation and migration