Transcription factor A, mitochondrial promotes lymph node metastasis and lymphangiogenesis in epithelial ovarian carcinoma.

Abstract

Background: Mitochondria play a central, multifunctional role in cancer progression. However, the mechanism of mitochondrial genes in epithelial ovarian cancer (EOC) remains unclear. This study aimed to screen candidate mitochondrial genes in EOC and then to investigate their biological functions and potential mechanisms.

Methods: We downloaded Gene Expression Omnibus RNA-seq profiles and identified mitochondrial differentially expressed genes in EOC by bioinformatics analysis. Transcription factor A, mitochondrial (TFAM) expression in EOC tissues was determined by immunohistochemistry. In vitro assays were applied to clarify TFAM function in EOC.

Results: The bioinformatics analysis results showed that the mitochondrial genes TFAM, HSPE1, and CYC1 were significantly upregulated (P < 0.05) in EOC, and their upregulation was associated with a poor prognosis. TFAM was highly expressed in EOC tissues and significantly associated with clinical stage (P = 0.004), lymph node metastasis (P = 0.043), and overall survival (P < 0.05). Silencing TFAM in EOC cells significantly inhibited cell proliferation and migration and induced cell apoptosis (P < 0.05).

Conclusion: TFAM promotes EOC cell secretion of VEGF-A, VEGF-C, VEGF-D, lymphangiogenesis, and EOC lymph node metastasis. Our results may provide new insights into the biological functions and potential mechanisms of TFAM in EOC, which might provide new targets for EOC diagnosis and treatment.