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Digestive Diseases and Sciences

Erschienen in:

12.01.2021 | Original Article

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

verfasst von: LiLi Zhao, Ning Ma, Gaihong Liu, Ni Mao, Fei Chen, Jiao Li

Erschienen in: Digestive Diseases and Sciences | Ausgabe 12/2021

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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.

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Titel: Lidocaine Inhibits Hepatocellular Carcinoma Development by Modulating circ_ITCH/miR-421/CPEB3 Axis
verfasst von: LiLi Zhao
Ning Ma
Gaihong Liu
Ni Mao
Fei Chen
Jiao Li
Publikationsdatum: 12.01.2021
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 12/2021
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-020-06787-1

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

Abstract

Background

Aims

Methods

Results

Conclusions

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Abstract

Background

Aims

Methods

Results

Conclusions

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