LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway

Abstract Background LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). Method qRT-PCR and Immunofluorescence were...

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Main Authors: Chao Lin, Tao Jiang, Changyong E, Lun Wang, Tong Chen, Xia Wang, Yien Xiang
Format: Article
Language:English
Published: BMC 2024-05-01
Series:Cancer Cell International
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Online Access:https://doi.org/10.1186/s12935-024-03380-8
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author Chao Lin
Tao Jiang
Changyong E
Lun Wang
Tong Chen
Xia Wang
Yien Xiang
author_facet Chao Lin
Tao Jiang
Changyong E
Lun Wang
Tong Chen
Xia Wang
Yien Xiang
author_sort Chao Lin
collection DOAJ
description Abstract Background LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). Method qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis. Results Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism. Conclusion CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.
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spelling doaj-art-29621b6bb731474c86e5b7e8d368b7a52025-08-20T03:01:38ZengBMCCancer Cell International1475-28672024-05-0124111210.1186/s12935-024-03380-8LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathwayChao Lin0Tao Jiang1Changyong E2Lun Wang3Tong Chen4Xia Wang5Yien Xiang6Hepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin UniversityHepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin UniversityHepatobiliary and Pancreatic Surgery, China-Japan Union Hospital of Jilin UniversityGastrointestinal Surgery, Affiliated Hospital of Zunyi Medical UniversityGastrointestinal Surgery, China-Japan Union Hospital of Jilin UniversityGeneral Surgery, China-Japan Union Hospital of Jilin UniversityHepatobiliary and Pancreatic Surgery, the Second Hospital of Jilin UniversityAbstract Background LncRNA colorectal neoplasia differentially expressed (CRNDE) was found to be an important regulator in many cancers. This project focuses on the function of CRNDE on macrophage metabolic reprogramming and Hepatocellular carcinoma (HCC). Method qRT-PCR and Immunofluorescence were used to analyze Arg-1, IL-10, CD163, CCL-18, CD206, and CRNDE expression in HCC tissues and macrophages. Western Blotting was used to analyze ERK and p-ERK expression. Edu assay, transwell assay and xenograft experiments were carried out to study cell viability, migrated and invasive capability. Immunohistochemical staining was used to evaluate Ki67 expression. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed for macrophages metabolites analysis. Results Arg-1, IL-10, CD163, CD206, and CRNDE were significantly up-regulated in HCC tissues, M2 macrophage and M0 macrophage with CRNDE overexpressed (OV-CRNDE-M0), which downregulated in M0 macrophage with CRNDE knockdown (sh-CRNDE-M0). The conditioned medium (CM) of M2 cells and OV-CRNDE-M0 cells promoted cell viability, invasion, and migration of HCC cells, the effect was reversed by sh-CRNDE-M0 cells CM. OV-CRNDE-M0 cells promoted tumor growth, Ki67 and CD206 expression in xenograft model. 61 metabolites were detected, of which 18 metabolites changed significantly in OV-CRNDE-M0 group compared to M0 group, with 9 upregulated and 9 downregulated. KEGG analysis showed the enrichment pathways were biosynthesis, glyoxylate and dicarboxylate metabolism. SMPDB analysis showed the enrichment pathways were hypoacetylaspartia, canavan disease, and aspartate metabolism. Conclusion CRNDE regulated the metabolic reprogramming of M2 macrophage via ERK pathway, which thereby contributed to HCC proliferation, migration, and invasion.https://doi.org/10.1186/s12935-024-03380-8CRNDEMacrophageMetabolic reprogrammingHepatocellular carcinoma
spellingShingle Chao Lin
Tao Jiang
Changyong E
Lun Wang
Tong Chen
Xia Wang
Yien Xiang
LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway
Cancer Cell International
CRNDE
Macrophage
Metabolic reprogramming
Hepatocellular carcinoma
title LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway
title_full LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway
title_fullStr LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway
title_full_unstemmed LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway
title_short LncRNA CRNDE promotes hepatoma cell proliferation by regulating the metabolic reprogramming of M2 macrophages via ERK pathway
title_sort lncrna crnde promotes hepatoma cell proliferation by regulating the metabolic reprogramming of m2 macrophages via erk pathway
topic CRNDE
Macrophage
Metabolic reprogramming
Hepatocellular carcinoma
url https://doi.org/10.1186/s12935-024-03380-8
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