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NCBP2 promotes colorectal cancer growth and metastasis by driving lipid droplet accumulation by stabilizing LIPG mRNA

ABSTRACT: RNA-binding proteins are critical for RNA processing and aberrantly expressed in colorectal cancer (CRC). In this study, by screening and bioinformatic analyses of the TCGA database and GSE20916 and GSE18105 datasets, NCBP2 was ultimately identified as a potential oncogene in CRC. We observed that NCBP2 was overexpressed in tumour tissues; its overexpression was correlated with CRC invasion and distant metastasis and indicated poorer survival in CRC patients. NCBP2 overexpression promoted the proliferation, migration and invasion of CRC cells in vitro and in vivo. Mechanistically, the NCBP2 protein stabilizes LIPG mRNA and increases LIPG expression via direct binding to m7G in the 5’-cap structure of LIPG mRNA. NCBP2 also facilitates lipid droplet accumulation in CRC cells in a LIPG-dependent manner. This study demonstrated that the NCBP2–LIPG–lipid droplet axis represents a new mechanism for CRC growth and distant metastasis and is a promising target for CRC treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270402 | GEO | 2024/08/30

REPOSITORIES: GEO

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Project description:Purpose: This study aimed to identify a novel biomarker or a target of treatment for colorectal cancer (CRC). Experimental Design: The expression profiles of cancer cells in 104 patients with CRC were examined using laser microdissection and oligonucleotide microarray analysis. Overexpression in CRC cells especially in patients with distant metastasis was a prerequisite to select candidate genes. The mRNA expression of candidate gene was investigated by quantitative reversetranscription polymerase chain reaction (RT-PCR) in 77 patients as a validation study. We analyzed the protein expression and localization of the candidate gene by immunohistochemical study, and investigated the relationship between the expression and the clinicopathological feature in 274 CRC patients. Results: We identified 6 genes as candidates related to distant metastasis in CRC patients by microarray analysis. Among these genes, Osteoprotegerin (OPG) is known to have an association with aggressiveness in several cancers through inhibiting apoptosis by neutralizing the function of tumor necrosis factor related apoptosis inducing ligand (TRAIL). The mRNA expression of OPG in cancer tissues was significantly higher in patients with distant metastasis than those without metastasis. The overexpression of OPG protein was significantly associated with worse overall survival and relapse free survival (RFS). Moreover, the overexpression of OPG protein was an independent risk factor for recurrence of CRC. Conclusion: The overexpression of OPG would be a predictive biomarker of recurrence and a target of the treatment for CRC. Total of 148 microarray datasets obtained from LCM and homogenized tissues of colorectal cancer patients were normalized using robust multi-array average (RMA) method under R 2.6.2 statistical software with affy package from BioConductor. Normalization was separately performed for LCM dataset and homogenized tissue dataset. The normalized gene expression levels were presented as log2-transformed values by RMA.

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NCBP2 promotes colorectal cancer growth and metastasis by driving lipid droplet accumulation by stabilizing LIPG mRNA

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