1. Family with sequence similarity 46 member a confers chemo-resistance to ovarian carcinoma via TGF-β/Smad2 signaling
- Author
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Suiying Liang, Lanying Li, Tian Gao, Yueyang Liu, Shanyang He, and Jianhui He
- Subjects
Ovarian Neoplasms ,Carcinoma ,Bioengineering ,General Medicine ,Smad2 Protein ,Biology ,Carcinoma, Ovarian Epithelial ,Applied Microbiology and Biotechnology ,Similarity (network science) ,Transforming Growth Factor beta ,Ovarian carcinoma ,Cell Line, Tumor ,Cancer research ,Humans ,Female ,Chemo resistance ,Transforming growth factor ,Sequence (medicine) ,Biotechnology ,Signal Transduction - Abstract
Purpose: Ovarian cancer is the most lethal malignancy with depressive 5-year survival rate, mainly due to patients with advanced stages experience tumor recurrence and resistance to the current chemotherapeutic agents. Thus, discovering the underlying molecular mechanisms involved in chemo-resistance is crucial for management of treatment to improve therapeutic outcomes. Methods: The protein and mRNA expression of FAM46A in ovarian cancer cell lines and patient tissues were determined using Real-time PCR and Western blot and IHC respectively. Functional assays, such as MTT, FACS assay used to determine the oncogenic role of FAM46A in human ovarian cancer progression. Furthermore, western blotting and luciferase assay were used to determine the mechanism of FAM46A promotes chemoresistance in ovarian cancer cells. Results: In the current study, we found overexpression of FAM46A expression in ovarian cancer patients demonstrated an aggressive phenotype and poor prognosis. Furthermore, FAM46A overexpression in ovarian cancer cells demonstrated higher CDDP resistance ability; however, inhibition of FAM46A sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. Mechanically, upregulation of FAM46A activated transforming growth factor-β (TGF-β)/Smad signaling and upregulated the levels of nuclear Smad2. Conclusions: Taken together, our results highlight the important oncogenic role of FAM46A in ovarian cancer progression and might provide a potential clinical target for patients with chemoresistant ovarian cancer.
- Published
- 2022