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

Life ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 8
Author(s):  
Daniela B. Vera ◽  
Allison N. Fredes ◽  
Maritza P. Garrido ◽  
Carmen Romero

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+2, 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.

1999 ◽  
Vol 15 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Ali Khalifa ◽  
Samar K. Kassim ◽  
Maha I. Ahmed ◽  
Salah T. Fayed

The role of transforming growth factor-β(TGF-β) and nitric oxide (NO) in ovarian neoplasia is still not clear. We studied the expression of TGF-βby enzyme immunoassay, and nitrates (as a stable end product of NO) in 127 ovarian tissues (36 normal, 37 benign, and 54 malignant). Ploidy status and synthetic phase fraction (SPF) were also assessed by flow cytometry. Mean ranks of TGF-β, nitrate, and SPF were significant among different groups (X2= 12.01, P = 0.0025, X2= 67.42, P = 0.000, X2= 9.06, P = 0.011 respectively). Nitrate mean ranks were significant among different FIGO stages of the disease (X2= 17.6, P = 0.000). A significant correlation was shown between TGF-â, and nitrate levels in all tissues (r = 0.24, P = 0.01), as well as in malignant tissues (r = 0.3, P = 0.026). Cutoff values were determined for both TGF-β(290 pg/mg protein), and nitrates (310 nmole/mg non protein nitrogenous substances). At these cut-offs, nitrates showed a sensitivity of 93% and 84% specificity for malignant versus normal cases, while TGF-βhad 76% sensitivity, and 82.4% specificity for poor versus good outcome. Patients with epithelial ovarian cancer were followed up for a total of 40 months. Survival analysis showed that patients with TGF-βabove the cut-off had worse prognosis (X2= 12.69, P = 0.004). The present results suggest that malignant transformation of ovarian tissues is associated with increased TGF-βand NO production. NO level is related to the development and progression of epithelial ovarian cancer, while high levels of TGF-βcould be of prognostic significance.


2017 ◽  
Vol 18 (3) ◽  
pp. 507 ◽  
Author(s):  
Rocío Retamales-Ortega ◽  
Lorena Oróstica ◽  
Carolina Vera ◽  
Paula Cuevas ◽  
Andrea Hernández ◽  
...  

2021 ◽  
Author(s):  
Jie Luo ◽  
Yuqiang Zhang ◽  
Ting Zheng ◽  
Yongping Jing ◽  
Rongyu Cao ◽  
...  

Abstract Background: This study aimed to explore the role of lncRNA DLGAP1-AS2 in ovarian cancer (OC). Methods: Expression of DLGAP1-AS2, mature miR-16 and miR-16 precursor in paired OC tissues and non-tumor tissues collected from 62 OC patients was determined by RT-qPCR. Correlations were analyzed by Pearson’s correlation coefficient. Overexpression of DLGAP1-AS2 was achieved in OC cell line UWB1.289 to explore the effects of DLGAP1-AS2 overexpression on the expression of mature miR-16 and miR-16 precursor by RT-qPCR. Transwell assays were performed to analyze the role of DLGAP1-AS2 and miR-16 in regulating the invasion and migration of UWB1.289 cells.Results: DLGAP1-AS2 was upregulated in OC and inversely correlated with mature miR-16, but not miR-16 precursor. In OC cells, DLGAP1-AS2 overexpression resulted in downregulated mature miR-16, but failed to significantly affect the expression of miR-16 precursor. Cell invasion and migration analysis showed that DLGAP1-AS2 overexpression reduced the inhibitory effects of miR-16 overexpression on cell invasion and migration.Conclusions: DLGAP1-AS2 may suppress the maturation of miR-16 to suppress cell invasion and migration of OC cells.


2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Lei Du ◽  
Cong-Rong Li ◽  
Qi-Feng He ◽  
Xiao-Hua Li ◽  
Lin-Fei Yang ◽  
...  

Abstract Objectives Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. Methods We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. Results First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. Conclusion Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.


2005 ◽  
Vol 97 (3) ◽  
pp. 870-878 ◽  
Author(s):  
John So ◽  
Feng-qiang Wang ◽  
Jason Navari ◽  
Jeremy Schreher ◽  
David A. Fishman

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