2. Academic Validation
  3. Lidocaine Inhibits Hepatocellular Carcinoma Development by Modulating circ_ITCH/miR-421/CPEB3 Axis

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

  • Dig Dis Sci. 2021 Dec;66(12):4384-4397. doi: 10.1007/s10620-020-06787-1.
LiLi Zhao 1,  Ning Ma 2,  Gaihong Liu 3,  Ni Mao 4,  Fei Chen 5,  Jiao Li 6
Affiliations

Affiliations

  • 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. [email protected].
PMID: 33433806 DOI: 10.1007/s10620-020-06787-1
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.

Keywords

CPEB3; Circ_itch; Hepatocellular carcinoma; Lidocaine; miR-421.

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