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

Abstract

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

Keywords

• circular RNA
• hsa_circ_0003998
• miR-326
• Notch1
• NSCLC