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Effect of SAP30 in breast cancer progression and metastasis (RNA-Seq)

ABSTRACT: Effect of SAP30 in breast cancer progression and metastasis (RNA-Seq)

PROVIDER: PRJNA893018 | ENA |

REPOSITORIES: ENA

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Effect of SAP30 in breast cancer progression and metastasis (RNA-Seq)

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Project description:To determine the roles of RBP2 in breast cancer metastasis, MDA-MD-231 cells were transfected with siRNAs against RBP2 or luciferase control, followed with gene expression microarray analysis and gene set enrichment analysis. These analyses revealed that RBP2 knockdown significantly decreased expression of genes linked to breast cancer metastasis to lung. Total RNA obtained from the breast cancer cell line MDA-MB231 72 hours after transfection with siRNA targeting KDM5A/RBP2/JARID1A, and targeting Luceferase gene as a control.

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Project description:Mitochondrial metabolism plays a central role in promoting cancer growth and metastatic progression. The transition between a hyperfused and fragmented mitochondrial network is termed mitochondrial dynamics and is important for many mitochondria-associated functions; however, little is known regarding how this process influences metastasis. Here, we show that breast cancer cells with low metastatic potential exhibit a more fused mitochondrial network compared to highly metastatic breast cancer cells. To examine whether a fused mitochondrial network could impair metastasis, we inhibited mitochondrial fission in metastatic breast cancer cells by individual genetic deletion of three key regulators of mitochondrial fission (Drp1, Fis1 and Mff) or pharmacological intervention using leflunomide, an anti-rheumatic drug. These cells displayed a fused mitochondrial network and limited survival under anoikis conditions, consistent with mitochondrial fusion limiting metastasis. Transcriptomics and metabolomics analyses revealed that mitochondrial fusion causes significant alterations in metabolic pathways and processes related to cell adhesion. Functional bioenergetics assays demonstrated that mitochondrial fusion limited the mitochondrial capacity of cancer cells. Mitochondrial fusion in breast cancer cells had no significant effect on primary tumor growth but almost completely ablated lung metastasis in vivo. Furthermore, the transcriptomics signature associated with enhanced mitochondrial fusion correlated with improved survival in patients with breast cancer. Overall, our findings highlight mitochondrial fusion as a therapeutic opportunity for breast cancer.

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