circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway

Abstract

Abstract Non-small cell lung cancer (NSCLC) accounts for 80% of total lung cancers, which are the main killer of cancer-related death worldwide. Circular RNA (circRNA) has been found to modulate NSCLC development. However, the role of circ_0000376 in NSCLC development has been underreported. The present work showed that circ_0000376 and 3-phos-phoinositide-dependent protein kinase-1 (PDPK1) expression were dramatically increased, but miR-545-3p was decreased in NSCLC tissues and cells. circ_0000376 expression was closely associated with lymph node metastasis, tumor-node-metastasis stage, and tumor size of NSCLC patients. circ_0000376 knockdown repressed NSCLC cell proliferation, migration, invasion, and glutaminolysis but induced cell apoptosis. Additionally, miR-545-3p bound to circ_0000376, and circ_0000376 regulated cell phenotypes by associating with miR-545-3p. MiR-545-3p also participated in NSCLC cell proliferation, migration, invasion, apoptosis, and glutaminolysis by targeting PDPK1. Further, circ_0000376 absence repressed tumor formation in vivo. Collectively, circ_0000376 regulated NSCLC cell tumor properties by the miR-545-3p/PDPK1 axis, suggesting that circ_0000376 could be employed as a therapeutic target for NSCLC.