LncRNA FAM225B Regulates PDIA4-Mediated Ovarian Cancer Cell Invasion and Migration via Modulating Transcription Factor DDX17

Abstract

Objective. This study aimed to explore the roles and mechanisms of lncRNA FAM225B and PDIA4 in ovarian cancer. Methods. RT-qPCR and Western blot assays were performed to detect the expression levels of the lncRNAs FAM225B, DDX17, and PDIA4 in the serum of patients with ovarian cancer and cell lines. Cells were transfected with lncRNA FAM225B- and PDIA4-related vectors to determine the malignant phenotypes using functional experiments. The mutual binding of lncRNA FAM225B and DDX17 was verified using RNA pull-down and RIP assays. Results. The expression of lncRNAs FAM225B and PDIA4 was decreased in the serum of patients with ovarian cancer and cell lines. Restoration of lncRNA FAM225B or PDIA4 reduced cell proliferation, migration, and invasion abilities and elevated the apoptosis rate, whereas suppression of lncRNA FAM225B or PDIA4 exhibited an inverse trend. RNA pull-down and RIP assays revealed a direct interaction between lncRNA FAM225B and DDX17. ChIP assay revealed a relationship between DDX17 and the PDIA4 promoter. LncRNA FAM225B and DDX17 positively regulate PDIA4 expression. Downregulation of PDIA4 expression counteracts the suppressive effect of lncRNA FAM225B overexpression in ovarian cancer cells. Conclusion. This research study supports the fact that lncRNA FAM225B in ovarian cancer can upregulate PDIA4 by directly binding to DDX17, inhibiting the activities of ovarian cancer cells.

New mechanism of LncRNA: In addition to act as a ceRNA

“…DDX17 as a transcription factor, binds to the PDIA4 promoter to promote transcription, and restoration of PDIA1 expression inhibits the malignant phenotype of ovarian cancer cells. Therefore, in ovarian cancer, lncRNA FAM225B promotes PDIA4 expression through DDX17, which in turn inhibits ovarian cancer progression [ 39 ].…”