Up-Regulation of FSTL3, Regulated by lncRNA DSCAM-AS1/miR-122-5p Axis, Promotes Proliferation and Migration of Non-Small Cell Lung Cancer Cells.

BACKGROUND

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.