LiLi Zhao1, Ning Ma2, Gaihong Liu3, Ni Mao4, Fei Chen5, Jiao Li6. 1. Department of Renal Medicine, The Third Affiliated Hospital of Jinzhou Medical University, 2 Section 5, Heping Road, Linghe District, Jinzhou City, Liaoning Province, China. 2. Department of Anesthesiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China. 3. Department of Anesthesiology, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369 Jingshi Road, Jinan City, Shandong Province, China. 4. Department of Neurology, 960th Hospital, People's Liberation Army, 25 Tianqiao District Normal Road, Jinan, Shandong Province, China. 5. Department of Drug Supply Station, Unit 32653 of the People's Liberation Army, No. 53-20, North Erxi Road, Zhonggong Street, Tiexi District, Shenyang, China. 6. Department of Anesthesiology, Cancer Hospital of China Medical University, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110042, Liaoning, China. xuanchao177069@126.com.
Abstract
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.
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.
Authors: Henning Hermanns; Markus W Hollmann; Markus F Stevens; Philipp Lirk; Timo Brandenburger; Tobias Piegeler; Robert Werdehausen Journal: Br J Anaesth Date: 2019-07-11 Impact factor: 9.166