Role of Mitochondria in Interplay between NGF/TRKA, miR-145 and Possible Therapeutic Strategies for Epithelial Ovarian Cancer

• Published in: Life (Basel, Switzerland) Switzerland), 2021-12, Vol.12 (1), p.8
• Main Authors: Vera, Daniela B, Fredes, Allison N, Garrido, Maritza P, Romero, Carmen
• Format: Article
• Language: English
• Subjects: Angiogenesis; Apoptosis; Autophagy; BAX protein; Bcl-2 protein; c-Myc protein; Calcium ions; Cancer; Cancer therapies; Cell death; Cell proliferation; Chemotherapy; Disease; epithelial ovarian cancer (EOC); Glucose; Growth factors; Homeostasis; Kinases; Medical prognosis; Metabolism; miRNA; Mitochondria; Mitochondrial DNA; Myc protein; Neoplasia; Nerve growth factor; nerve growth factor (NGF); neurotrophins (NTs); Ovarian cancer; oxidative phosphorylation (OXPHOS); Pathogenesis; Patients; Proteins; Review; Therapeutic targets; TrkA protein; Tropomyosin; Tropomyosin kinase; tropomyosin receptor kinase A (TRKA); Tumors; Vascular endothelial growth factor
• ISSN: 2075-1729; 2075-1729
• DOI: 10.3390/life12010008

Ovarian cancer is the most lethal gynecological neoplasm, and epithelial ovarian cancer (EOC) accounts for 90% of ovarian malignancies. The 5-year survival is less than 45%, and, unlike other types of cancer, the proportion of women who die from this disease has not improved in recent decades. Nerve growth factor (NGF) and tropomyosin kinase A (TRKA), its high-affinity receptor, play a crucial role in pathogenesis through cell proliferation, angiogenesis, invasion, and migration. NGF/TRKA increase their expression during the progression of EOC by upregulation of oncogenic proteins as vascular endothelial growth factor (VEGF) and c-Myc. Otherwise, the expression of most oncoproteins is regulated by microRNAs (miRs). Our laboratory group reported that the tumoral effect of NGF/TRKA depends on the regulation of miR-145 levels in EOC. Currently, mitochondria have been proposed as new therapeutic targets to activate the apoptotic pathway in the cancer cell. The mitochondria are involved in a myriad of functions as energy production, redox control, homeostasis of Ca , and cell death. We demonstrated that NGF stimulation produces an augment in the Bcl-2/BAX ratio, which supports the anti-apoptotic effects of NGF in EOC cells. The review aimed to discuss the role of mitochondria in the interplay between NGF/TRKA and miR-145 and possible therapeutic strategies that may decrease mortality due to EOC.