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CCDC12 regulates selective shear of RBM47 to promote breast cancer progression

ABSTRACT: Purpose: TThe Coiled coil domain containing (CCDC) protein is an egg that is closely related to malignant tumors. Methods:Breast cancer cells MDA-MB-231(NC), MDA-MB-231(shCCDC12)were deeply sequenced by Illumina sequencing platform (HISEQ2500) in triplices. Genes with adjusted p values < 0.05 and |foldChange| > 2 were defined as differential expression Genes (DEGs) and enriched with GO and KEGG. Several essential genes were validated by qRT-PCR using QuantStudio 5 (Thermo Fisher) and SYBR Green assays. The White Family. Studies have shown that CCDC protein is abnormally expressed in malignant tumors and changes cell proliferation cycle by regulating cell transcription factors Stage, promote the invasion and metastasis of malignant tumor cells. How does CCDC12 as a shear gene affect the biology of breast cancer Scientific activity remains to be further studied. Results: To verify the biological properties of CCDC12 in breast cancer, we studied breast cancer MDA-MB-231 knocked down the expression of CCDC12 in the cell line, and previous studies showed that TCGA and CPTAC database scores The mRNA and protein expression levels of CCDC12 gene were significantly up-regulated in normal breast cancer tissues compared with tumor tissues. Knocking down the expression level of CCDC12 in MDA-MB-231 cells can significantly inhibit cell growth, proliferation and migration. In tumor formation experiments in nude mice, low expression of CCDC12 can inhibit tumor growth. Knock down CCDC12 on MDA-MB-231 Splicing event analysis was performed by cell transcriptome sequencing, and differential analysis found that CCDC12 expression was differentially induced in breast cancer cells The RNA binding motif protein 47 (RBM47) Skipped exon, causing RMB47 to open The structure of the reading frame changes, altering gene function. Conclusions:This study confirmed that CCDC12 regulates the invasion and metastasis of breast cancer cells by regulating the variable shear of RBM47, inducing cell cycle arrest and promoting cell apoptosis. The results of RNA-Seq were consistent with our in vitro and in vivo experiments.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267326 | GEO | 2024/12/31

REPOSITORIES: GEO

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Project description:Since bone metastatic breast cancer is an incurable disease, causing significant morbidity and mortality, understanding of the underlying molecular mechanisms would be highly valuable. Here, we describe in vitro and in vivo evidence for the importance of serine biosynthesis in the metastasis of breast cancer to bone. We first characterized the bone metastatic propensity of the MDA-MB-231(SA) cell line variant as compared to the parental MDA-MB-231 cells by radiographic and histological observations in the inoculated mice. Genome-wide gene expression profiling of this isogenic cell line pair revealed that all the three genes involved in the L-serine biosynthesis pathway, phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and phosphoserine phosphatase (PSPH) were upregulated in the highly metastatic variant. This pathway is the primary endogenous source for L-serine in mammalian tissues. Consistently, we observed that the proliferation of MDA-MB-231(SA) cells in serine-free conditions was dependent on PSAT1 expression. In addition, we observed that L-serine is essential for the formation of bone resorbing human osteoclasts and may thus contribute to the vicious cycle of osteolytic bone metastasis. High expression of PHGDH and PSAT1 in primary breast cancer was significantly associated with decreased relapse-free and overall survival of patients and malignant phenotypic features of breast cancer. In conclusion, high expression of serine biosynthesis genes in metastatic breast cancer cells and the stimulating effect of L-serine on osteoclastogenesis and cancer cell proliferation indicate a functionally critical role for serine biosynthesis in bone metastatic breast cancer and thereby an opportunity for targeted therapeutic interventions. Parental MDA-MB-231 cells and MDA-MB-231(SA) cells were cultured in cell culture flasks. RNA was isolated in order to compare the gene expression profiles of these cell variants. Total of two samples. No replicates.

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CCDC12 regulates selective shear of RBM47 to promote breast cancer progression

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