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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2024

Open Access 01-12-2024 | Gallbladder Cancer | Research

Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis

Authors: Yang Yang, Huaifeng Li, Ke Liu, Lu Zou, Shanshan Xiang, Yajun Geng, Xuechuan Li, Shimei Qiu, Jiahua Yang, Xuya Cui, Lin li, Yang Li, Weijian Li, Siyuan Yan, Liguo Liu, Xiangsong Wu, Fatao Liu, Wenguang Wu, Shili Chen, Yingbin Liu

Published in: Journal of Translational Medicine | Issue 1/2024

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Abstract

Background

The progression of gallbladder cancer (GBC) is accompanied by abnormal fatty acid β-oxidation (FAO) metabolism. Different types of lipids perform various biological functions. This study aimed to determine the role of acyl carnitines in the molecular mechanisms of GBC progression.

Methods

Distribution of lipids in GBC was described by LC–MS-based lipidomics. Cellular localization, expression level and full-length of lncBCL2L11 were detected using fluorescence in situ hybridization (FISH) assays, subcellular fractionation assay and 5′ and 3′ rapid amplification of the cDNA ends (RACE), respectively. In vitro and in vivo experiments were used to verify the biological function of lncBCL2L11 in GBC cells. Methylated RNA Immunoprecipitation (MeRIP) was performed to detect the methylation levels of lncBCL2L11. RNA pull-down assay and RNA immunoprecipitation (RIP) assay were used to identify lncBCL2L11 interacting proteins. Co-Immunoprecipitation (Co-IP) and Western blot assay were performed to validate the regulatory mechanism of lncBCL2L11 and THO complex.

Results

Acylcarnitines were significantly up-regulated in GBC tissues. High serum triglycerides correlated to decreased survival in GBC patients and promoted tumor migration. LncBCL2L11 was identified in the joint analysis of highly metastatic cells and RNA sequencing data. LncBCl2L11 prevented the binding of THOC6 and THOC5 and causes the degradation of THOC5, thus promoting the accumulation of acylcarnitines in GBC cells, leading to the malignant progression of cancer cells. In addition, highly expressed acylcarnitines stabilized the expression of lncBCL2L11 through N6-methyladenosine methylation (m6A), forming a positive feedback regulation in tumor dissemination.

Conclusions

LncBCL2L11 is involved in gallbladder cancer metastasis through FAO metabolism. High lipid intake is associated with poor prognosis of GBC. Therefore, targeting lncBCL2L11 and its pathway-related proteins or reducing lipid intake may be significant for the treatment of GBC patients.
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Metadata
Title
Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis
Authors
Yang Yang
Huaifeng Li
Ke Liu
Lu Zou
Shanshan Xiang
Yajun Geng
Xuechuan Li
Shimei Qiu
Jiahua Yang
Xuya Cui
Lin li
Yang Li
Weijian Li
Siyuan Yan
Liguo Liu
Xiangsong Wu
Fatao Liu
Wenguang Wu
Shili Chen
Yingbin Liu
Publication date
01-12-2024
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2024
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-024-05091-0

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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