Dataset Information

Exosomal circPABPC1 promotes colorectal cancer liver metastases by regulating HMGA2 in the nucleus and BMP4/ADAM19 in the cytoplasm.

ABSTRACT: Liver metastasis is the leading cause of death in colorectal carcinoma (CRC). However, little is known about the mechanisms of transferring effector messages between the primary tumor and the site of metastasis. Exosomes provide a novel transfer message method, and exosomal circular RNAs (circRNAs) play critical regulatory roles in cancer biology. In this study, the results showed that the expression of circPABPC1 was aberrantly upregulated in CRC tissues and exosomes. Exosomal circPABPC1 was considered an oncogene by functional experimental analysis in vitro and in vivo. Mechanistically, circPABPC1 recruited KDM4C to the HMGA2 promoter, reduced its H3K9me3 modification and initiated the transcription process in the nucleus. Moreover, cytoplasmic circPABPC1 promoted CRC progression by protecting ADAM19 and BMP4 from miR-874-/miR-1292-mediated degradation. Our findings indicated that exosomal circPABPC1 is an essential regulator in CRC liver metastasis progression by promoting HMGA2 and BMP4/ADAM19 expression. CircPABPC1 is expected to be a novel biomarker and antimetastatic therapeutic target in CRC.

SUBMITTER: Li Y

PROVIDER: S-EPMC9308786 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundGrowing evidence has proved that Forkhead box protein 3 (FOXP3), which is a master regulatory gene in the development and function of regulatory T-cells, is expressed in human cancer cells. This expression indicates the crucial role FOXP3 takes up as the disease progresses. However, its role in colorectal cancer (CRC) liver metastasis is still mostly unknown. This study set out to explore the molecular characteristics of FOXP3 in driving the liver metastasis within CRC.MethodsWe downloaded the RNA-seq data from the GSE50760. Weighted gene co-expression network analysis (WGCNA)WGCNA and RNA-Seq analysis were applied to find the key gene network associated with colorectal cancer liver metastasis. Then we performed pathway enrichment analysis on liver metastasis-associated gene set. Immunohistochemistry, in vitro and in vivo studies were conducted to test expression and function of FOXP3 in CRC tissues and liver metastasis tissues. Non-targeted metabolomics analysis was performed to identify the alteration of FOXP3 expression in metabolites of colorectal cancer liver metastasis. Western blot was performed to confirm changes of matrix metalloproteinase 9MMP9 expression were downstream events of S-adenosyl-methionine (SAM).ResultsWe found that FOXP3 and MMP9 exhibited co-expression relationships and affected liver metastasis in CRC. Upregulation of FOXP3 promotes cell migration and invasion in CRC, which suggests a pro-cancer effect. Moreover, metabolomics analysis showed that knockdown of FOXP3 significantly reduced SAM levels, and changes of MMP9 expression were downstream events of SAM, which is concentration-dependent. Besides, The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Western blot analysis confirmed that overexpression of FOXP3 activates the Wnt pathway to promote colon cancer metastasis.ConclusionsOur results altogether suggested that FOXP3 expression inhibited the SAM cycle to reduce SAMe levels, resulting in altered MMP9 expression and helped CRC liver metastasis.

Dataset Information

Exosomal circPABPC1 promotes colorectal cancer liver metastases by regulating HMGA2 in the nucleus and BMP4/ADAM19 in the cytoplasm.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets