PHD finger protein 20-like protein 1 (PHF20L1) in ovarian cancer: from its overexpression in tissue to its upregulation by the ascites microenvironment

Abstract

Background Ovarian cancer is the most aggressive gynecological malignancy. Transcriptional regulators impact the tumor phenotype and, consequently, clinical progression and response to therapy. PHD finger protein 20-like protein 1 (PHF20L1) is a transcriptional regulator with several isoforms, and studies on its role in ovarian cancer are limited. We previously reported that PHF20L1 is expressed as a fucosylated protein in SKOV-3 cells stimulated with ascites from patients with ovarian cancer. Methods We decided to analyze the expression of PHF20L1 in ovarian cancer tissues, determine whether a correlation exists between PHF20L1 expression and patient clinical data, and analyze whether ascites can modulate the different isoforms of this protein. Ovarian cancer biopsies from 29 different patients were analyzed by immunohistochemistry, and the expression of the isoforms in ovarian cancer cells with or without exposure to the tumor microenvironment, i.e., the ascitic fluid, was determined by western blotting assays. Results Immunohistochemical results suggest that PHF20L1 exhibits increased expression in sections of tumor tissues from patients with ovarian cancer and that higher PHF20L1 expression correlates with shorter progression-free survival and shorter overall survival. Furthermore, western blotting assays determined that protein isoforms are differentially regulated in SKOV-3 cells in response to stimulation with ascites from patients with epithelial ovarian cancer. Conclusion The results suggest that PHF20L1 could play a relevant role in ovarian cancer given that higher PHF20L1 protein expression is associated with lower overall patient survival.

Overexpression of Fut 2, 4, and 8, and nuclear localization of Fut 4 in ovarian cancer cell lines induced by ascitic fluids from epithelial ovarian cancer patients

“…For example, TGF‐β, a growth factor present in most AFs, is directly or indirectly associated with promoting the proliferation of ovarian cancer cells (Puiffe et al, 2007), and in emphysema‐like phenotype in core fucosa‐deficient mice (Wang et al, 2005). On the other hand, the increase in total fucosylation was a generalized effect of the five AFs on the three cell lines, as has been previously reported by our group on cell surface fucosylation and tissues derived from tumors (Alberto‐Aguilar et al, 2022; Villegas‐Pineda et al, 2015), a process that has been poorly studied in ovarian cancer. Epidermal Growth Factor (EGF) is also a reported factor in AF (Maihle et al, 2002), and has been shown to participate in the progression of ovarian cancer.…”

“…It has been reported that fucosylation could vary between cell types and tissues (Alberto‐Aguilar et al, 2022). The presence of highly fucosylated antigens expressed on the surface of transformed cells is attributed to increased expression of FUTs and correlates with poor prognosis in colorectal cancer (Nakagoe et al, 2000; Puiffe et al, 2007).…”

Deciphering the dual roles of PHD finger proteins from oncogenic drivers to tumor suppressors

“…Additionally, PHF20L1 influences the tumor landscape by altering transcriptional dynamics, significantly impacting clinical outcomes and therapy responsiveness in ovarian cancer. The study underscores PHF20L1's potential as a therapeutic target, given its correlation with diminished patient survival rates (Alberto-Aguilar et al, 2022).…”

Expression Profiles and Bioinformatic Analysis of Circular RNAs in Db/Db Mice with Cardiac Fibrosis

“… 21 A previous study found that the expression of PHF20L1 was increased in tumor tissue sections of patients with ovarian cancer. 22 Based on the ceRNA regulatory network in Figure 5A , circPHF20L1/miR-29a-3p/Col6a2 may play a regulatory role in the development of myocardial fibrosis in DCM. The overexpression of circCLASP1, the third upregulated circRNA in the present study, greatly enhanced the stimulating effects of Huaier-induced immunogenic cell death.…”