Impact of mitochondrial transcription factor A expression on the outcomes of ovarian, endometrial and cervical cancers

Abstract

Gynecologic cancers, including endometrial, ovarian, and cervical cancers, are the leading causes of cancer-related mortality in women worldwide. Mitochondrial transcription factor A (TFAM) has been demonstrated playing critical roles in the development of tumors. However, the clinical relationship of TFAM expression in gynecologic cancers requires further clarification. Our results showed gynecologic cancer cells are highly expressed TFAM in both protein and RNA levels compared to normal cells. The TCGA dataset revealed that TFAM gene expression is higher in most of the solid tumors than the expression of the known oncogenes (e.g., TP53, BRCA1, and BRCA2). The dataset also suggested a high expression of TFAM in primary and recurrent tumor sites in gynecologic cancers compared to the adjacent normal tissues. Besides, the subcellular fractionation results indicated that the main form of TFAM in cells is chromatin-binding proteins. Further immunohistochemistry study showed that the overexpression of TFAM in tumor tissues is associated with the patient’s advanced clinicopathological parameters. The Kaplan-Meier analysis demonstrated that high TFAM expression is a potential prognostic prediction marker for the patient’s survival. Furthermore, we observed that downregulated TFAM expression with siRNA suppresses cell proliferation, colony formation, migration, and invasion ability. Taken together, our findings demonstrated that TFAM is highly expressed in cancer cell lines and tumor tissues of gynecologic cancers. The majority of TFAM protein is binding to chromatin in cells, and downregulation of TFAM suppresses cell proliferation, colony formation, migration, and invasion. High level of TFAM in tumor tissues is related to an unfavorable overall survival and disease-free survival in patients with endometrial, ovarian, and cervical cancers, which can serve as a promising prognostic predictive biomarker and a potential therapeutic target.