RESUMO
Circular RNAs (circRNAs) play a crucial regulatory role in malignant tumor metastasis. This study focused on the role of bone metastasis-related circRBMS3 in breast cancer. Two circRNA microarray datasets were obtained from the GEO database and overlapped bone metastasis-related circRNAs in breast cancer. CircRBMS3 expression was validated in bone metastasis tissues by RT-qPCR. Cellular CCK-8 assay and Transwell assays were performed to measure the effect of circRBMS3 in breast cancer cells. Bioinformatic analyses were performed to identify the binding miRNAs of circRBMS3 and downstream mRNAs. Online database STRING and Cytoscape software were used to analyze PPI interaction and conduct the ceRNA network. GEO database analysis showed that circRBMS3 was one of the upregulated circRNAs among all the metastatic cells. CircRBMS3 was increased in bone metastasis breast cancer tissues compared to non-bone metastasis tissues and associated with poor 3-year overall survival. CircRBMS3 knockdown repressed breast cancer cell proliferation, migration, and invasion, as well as bone resorption gene and osteoclast phenotype gene expression. CircRBMS3 was found to bind withmiR-654-3p. Subsequently, downstream mRNAs were predicted, and the circRBMS3 miR-654-3p-mRNA network was established. In conclusion, circRBMS3 expression was upregulated in bone metastasis breast cancer and might be a potential prognostic marker for patients. Silencing circRBMS3 restrained breast cancer cell proliferation, migration, and invasion, as well as associated with bone metastasis. The circRBMS3-miR-654-3p-mRNAs network elucidated potential mechanisms underlying bone metastasis in breast cancer.
Assuntos
Neoplasias Ósseas , Neoplasias da Mama , Movimento Celular , Proliferação de Células , Biologia Computacional , MicroRNAs , RNA Circular , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias Ósseas/secundário , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Feminino , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , RNA/metabolismo , RNA/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Regulação para CimaRESUMO
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Mounting evidence showed that circular RNAs (circRNAs) play critical roles in human malignancy. However, the knowledge about circRNAs in GC is still unclear. In the current study, high throughput microarray assay showed that circRBMS3 was upregulated in GC tissues, which was further confirmed by quantitative reverse transcription polymerase chain reaction. Correlation analysis revealed that high circRBMS3 expression was associated with advanced TNM stage, depth of invasion, and lymph-node metastasis. Kaplan-Meier analysis indicated that GC patients with high circRBMS3 expression have a poor overall survival (OS). Function assays showed that circRBMS3 silencing reduced GC cells proliferation and invasion in vitro, and inhibited the tumor growth in vivo. Mechanistically, we found that miR-153 could act as a target of circRBMS3. Subsequently, we showed that circRBMS3 promoted snail family zinc finger 1 (SNAI1) expression via inhibiting miR-153 in GC cells. Collectively, these results suggested that circRBMS3 promoted GC cells proliferation and invasion via regulating miR-153/SNAI1 axis.