Hsa_circ_0003998 promotes cell proliferation and invasion by targeting miR-326 in non-small cell lung cancer.

Background: Circular RNAs represent a new class of noncoding RNAs involved in the development of cancer. However, little is known about their role in non-small cell lung cancer (NSCLC).

Methods: We examined hsa_circ_0003998 levels in 60 NSCLC tissues by quantitative real-time polymerase chain reaction and analyzed the clinicopathologic significance of hsa_circ_0003998 expression. The effect of small interfering RNA-mediated hsa_circ_0003998 knockdown on proliferation and invasion was analyzed in A549 and H1299 cells in vitro. Moreover, the target genes of hsa_circ_0003998 were further explored by bioinformatic analysis, dual luciferase reporter assays, and rescue experiments.

Results: Hsa_circ_0003998 upregulation was associated with larger tumor size and lymph node metastasis and also correlated with shorter overall survival of NSCLC patients. Functional experiments showed knockdown of hsa_circ_0003998 restrained cell proliferation and invasion in NSCLC cells. In particular, hsa_circ_0003998 upregulated the expression of miR-326 target gene Notch1 through sponging miR-326. Furthermore, the tumor-inhibiting effect of hsa_circ_0003998 silencing was blocked by miR-326 inhibitor.

Conclusion: hsa_circ_0003998/miR-326/Notch1 pathway regulates the progression of NSCLC.