Lidocaine represses the malignant behavior of lung carcinoma cells via the circ_PDZD8/miR-516b-5p/GOLT1A axis.

Abstract

Lung carcinoma is the most prevalent malignancy in adults. Lidocaine (Lido) has been confirmed to exert an anti-tumor role in many human cancers. However, the role and underlying mechanism of Lido in lung carcinoma remain poorly understood. Cell proliferation ability, migration, invasion, and apoptosis were measured by Colony formation, 5-ethynyl-2'-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), transwell, and flow cytometry assays. Circ_PDZD8, microRNA-516b-5p (miR-516b-5p), and Golgi transport 1A (GOLT1A) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Protein levels of proliferating cell nuclear antigen (PCNA) and GOLT1A were examined by western blot assay. The binding relationship between miR-516b-5p and circ_PDZD8 or GOLT1A was predicted by circular RNA Interactome or Starbase 3.0 and then verified by a dual-luciferase reporter assay. The biological roles of circ_PDZD8 and Lido on lung carcinoma cell growth were examined by the xenograft tumor model in vivo. Lido suppressed proliferation, migration, invasion, and induced apoptosis in lung carcinoma cells. Circ_PDZD8 and GOLT1A were increased, miR-516b-5p was decreased in lung carcinoma tissues and cell lines. Their expression presented the opposite trend in Lido-triggered lung carcinoma cells. Circ_PDZD8 might overturn the repression of Lido on cell growth ability and metastasis in this tumor. Mechanically, circ_PDZD8 might regulate GOLT1A expression by sponging miR-516b-5p. Circ_PDZD8 weakened the anti-lung carcinoma effect of Lido in vivo. Circ_PDZD8 might mitigate the inhibitory effect of Lido on tumor cell malignancy by modulating the miR-516b-5p/GOLT1A axis, providing a novel insight for lung carcinoma treatment.