Department of Emergency and Critical Care Medicine, Jinshan Hospital, Fudan University, Shanghai, China.
Department of Obstetrics and Gynecology, Jinshan Hospital, Fudan University, Shanghai, China.
Clinics (Sao Paulo). 2022 Oct 23;77:100122. doi: 10.1016/j.clinsp.2022.100122. eCollection 2022.
Tripartite Motif 47 (TRIM47) protein plays a prominent role in many cancers. This study aimed to investigate the biological roles of TRIM47 in ovarian cancer.
TRIM47 was knocked down and overexpressed in ovarian cancer cell lines SKOV3 and OVCAR3, and the effects on proliferation, clone formation, apoptosis, invasion, and growth of xenograft tumors in nude mice were determined. The expression levels of the selected candidates were tested by western blotting and quantitative real-time PCR.
TRIM47 knockdown suppressed proliferation and encourages apoptosis of ovarian cancer cells. Similarly, TRIM47 knockdown suppressed ovarian cancer cell invasion, migration, and epithelial-mesenchymal transition. Ovarian cancer cell xenograft assays demonstrated that TRIM47 knockdown significantly inhibited tumor growth. Mechanistically, TRIM47 knockdown suppressed STAT3 phosphorylation and the expression of several downstream genes, including MCL-1, MMP2, and c-MYC. Silencing of STAT3 partially prevented TRIM47-induced tumor cell proliferation and invasion.
The present study's findings demonstrate that by activating STAT3 signaling, TRIM47 functions as an oncogene in ovarian cancer. TRIM47, therefore, appears to be a potential target for ovarian cancer prevention and/or therapy.
三基序蛋白 47（TRIM47）蛋白在许多癌症中发挥着重要作用。本研究旨在探讨 TRIM47 在卵巢癌中的生物学作用。
在卵巢癌细胞系 SKOV3 和 OVCAR3 中敲低和过表达 TRIM47，检测其对细胞增殖、克隆形成、凋亡、侵袭和裸鼠移植瘤生长的影响。通过 Western blot 和定量实时 PCR 检测候选物的表达水平。
TRIM47 敲低抑制卵巢癌细胞的增殖并促进其凋亡。同样，TRIM47 敲低抑制卵巢癌细胞的侵袭、迁移和上皮间质转化。卵巢癌细胞移植瘤实验表明，TRIM47 敲低显著抑制肿瘤生长。机制上，TRIM47 敲低抑制 STAT3 磷酸化和几个下游基因的表达，包括 MCL-1、MMP2 和 c-MYC。STAT3 的沉默部分阻止了 TRIM47 诱导的肿瘤细胞增殖和侵袭。
本研究结果表明，TRIM47 通过激活 STAT3 信号通路在卵巢癌中发挥癌基因的作用。因此，TRIM47 似乎是预防和/或治疗卵巢癌的潜在靶点。
