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Lidocaine Suppresses Gastric Cancer Development Through Circ_ANO5/miR-21-5p/LIFR Axis

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Abstract

Background

Lidocaine has been manifested to exert anti-tumor role in gastric cancer (GC) progression. However, the action mechanism by which Lidocaine functions in GC has not been fully elucidated.

Aim

The study aimed to reveal the molecular mechanism of Lidocaine in GC progression.

Methods

Cell clonogenicity and viability were assessed by colony formation and methyl thiazolyl tetrazolium assays, respectively. Transwell assay was employed to detect cell migration and invasion. Flow cytometry was implemented to monitor cell apoptosis. Relative expression of circular RNA ANO5 (circ_ANO5), microRNA (miR)-21-5p and Leukemia inhibitory factor receptor (LIFR) was examined by quantitative reverse transcription-polymerase chain reaction. Western blot assay was performed to analyze the levels of LIFR and cell metastasis-related proteins. The target relationship between miR-21-5p and circ_ANO5 or LIFR was confirmed by dual-luciferase reporter assay. In addition, xenograft model was established to explore the role of Lidocaine in vivo.

Results

Lidocaine inhibited cell proliferation, migration and invasion, while promoted apoptosis of GC cells. Lidocaine upregulated circ_ANO5 and LIFR expression, but downregulated miR-21-5p expression in GC cells. Additionally, expression of circ_ANO5 and LIFR was decreased, while miR-21-5p expression was increased in GC cells. Circ_ANO5 depletion or miR-21-5p overexpression attenuated Lidocaine-induced anti-proliferative and anti-metastatic effects on GC cells. Circ_ANO5 could sponge miR-21-5p, and miR-21-5p targeted LIFR. Moreover, Lidocaine suppressed the tumor growth in vivo.

Conclusion

Lidocaine might GC cell malignancy by modulating circ_ANO5/miR-21-5p/LIFR axis, highlighting a novel insight for GC treatment.

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Authors and Affiliations

  1. Department of Anesthesiology, Shenzhen Longhua District Central Hospital, Shenzhen, 518110, China

    Enjian Guan

  2. Department of UI Trasonography, Weihaiwei People’s Hospital, Weihai, 264200, China

    Hongrong Liu

  3. Department of Medical Imaging, Shenzhen Longhua District Central Hospital, 187 Guanlan Avenue, Longhua District, Shenzhen, 518110, China

    Ning Xu

Authors
  1. Enjian Guan
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  2. Hongrong Liu
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  3. Ning Xu
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Contributions

Enjian Guan supervised the study; conducted the experiments; drafted the manuscript; collected and analyzed the data. Hongrong Liu contributed the methodology and edited the manuscript. Ning Xu was responsible for visualization, conceptualization and validation. All authors read and approved the final manuscript.

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Correspondence to Ning Xu.

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Guan, E., Liu, H. & Xu, N. Lidocaine Suppresses Gastric Cancer Development Through Circ_ANO5/miR-21-5p/LIFR Axis. Dig Dis Sci 67, 2244–2256 (2022). https://doi.org/10.1007/s10620-021-07055-6

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