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Current Gene Therapy

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ISSN (Print): 1566-5232
ISSN (Online): 1875-5631

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Research Article

FIGNL1 Promotes Hepatocellular Carcinoma Formation via Remodeling ECM-receptor Interaction Pathway Mediated by HMMR

Author(s): Jiabei Wang, Linmao Sun, Yao Liu* and Yunguang Zhang*

Volume 24, Issue 3, 2024

Published on: 31 October, 2023

Page: [249 - 263] Pages: 15

DOI: 10.2174/0115665232274223231017052707

Price: $65

Abstract

Background: The development of novel biomarkers is crucial for the treatment of HCC. In this study, we investigated a new molecular therapeutic target for HCC. Fidgetin-like 1 (FIGNL1) has been reported to play a vital role in lung adenocarcinoma. However, the potential function of FIGNL1 in HCC is still unknown.

Objective: This study aims to investigate the key regulatory mechanisms of FIGNL1 in the formation of HCC.

Methods: The regulatory effect of FIGNL1 on HCC was studied by lentivirus infection. In vitro, the effects of FIGNL1 on the proliferation, migration and apoptosis of cells were investigated by CCK8, colony formation assay, transwell and flow cytometry. Meanwhile, the regulation of FIGNL1 on HCC formation in vivo was studied by subcutaneous transplanted tumors. In addition, using transcriptome sequencing technology, we further explored the specific molecular mechanism of FIGNL1 regulating the formation of HCC.

Results: Functionally, we demonstrated that FIGNL1 knockdown significantly inhibited HCC cell proliferation, migration and promoted cell apoptosis in vitro. Similarly, the knockdown of FIGNL1 meaningfully weakened hepatocarcinogenesis in nude mice. Transcriptome sequencing revealed that FIGNL1 affected the expression of genes involved in extracellular matrix-receptor (ECM-receptor) interaction pathway, such as hyaluronan mediated motility receptor (HMMR). Further validation found that overexpression of HMMR based on knockdown FIGNL1 can rescue the expression abundance of related genes involved in the ECM-receptor interaction pathway.

Conclusion: Our study revealed that FIGNL1 could modulate the ECM-receptor interaction pathway through the regulation of HMMR, thus regulating the formation of HCC.

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