Lidocaine Inhibits Hepatocellular Carcinoma Development by Modulating circ_ITCH/miR-421/CPEB3 Axis.

Background: Lidocaine plays an anticancer role in hepatocellular carcinoma. Nevertheless, the mechanism of lidocaine in hepatocellular carcinoma remains largely unclear.
Aims: This study aims to assess the function of lidocaine and explore the potential regulatory mechanism.
Methods: Hepatocellular carcinoma cells were challenged via lidocaine. Cell proliferation, apoptosis, migration, and invasion were detected via colony formation, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, flow cytometry, Western blot, and transwell analyses. Circular RNA itchy E3 ubiquitin protein ligase (circ_ITCH), microRNA-421 (miR-421), and cytoplasmic polyadenylation element-binding protein 3 (CPEB3) abundances were detected via quantitative reverse transcription polymerase chain reaction or Western blot. The relationship between miR-421 and circ_ITCH or CPEB3 was tested via dual-luciferase reporter analysis. The role of circ_ITCH in lidocaine-challenged cell growth in vivo was assessed via xenograft model.
Results: Lidocaine inhibited hepatocellular carcinoma cell proliferation by decreasing colony formation and cell viability. Lidocaine suppressed hepatocellular carcinoma cell migration and invasion and promoted apoptosis. circ_ITCH and CPEB3 levels were decreased in hepatocellular carcinoma tissues and cells, and were restored in cells via lidocaine treatment. circ_ITCH knockdown weakened the suppressive effect of lidocaine on hepatocellular carcinoma development, which was abolished via CPEB3 overexpression. circ_ITCH could modulate CPEB3 by competitively binding with miR-421. miR-421 knockdown mitigated the effect of circ_ITCH silence in lidocaine-challenged cells. circ_ITCH knockdown increased xenograft tumor growth.
Conclusions: Lidocaine represses hepatocellular carcinoma cell proliferation, migration, and invasion and promotes apoptosis via regulating circ_ITCH/miR-421/CPEB3 axis, indicating a new insight into the mechanism of lidocaine in hepatocellular carcinoma.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)