Summary: | Wanjun Yu,1,2 Hao Jiang,2 Huihui Zhang,2 Jipeng Li1 1Department of Central Laboratory, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, China; 2Department of Respiratory and Critical Care Medicine, Yinzhou People’s Hospital, Yinzhou Hospital Affiliated to Medical School of Ningbo University, Ningbo 315040, China 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. Keywords: circular RNA, hsa_circ_0003998, miR-326, Notch1, NSCLC
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