Meng Fanling, Ding Jing, Xu Wei, Luo Chang, Chen Xihai, Zhang Ruichun, Sui Lin, Hu Yuanlong, Liu Shuang, Shi Guangyue, He Yunlong, Ning Xin, Ma Rong, Huang Ning
Department of Gynecology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Family Planning, Harbin Red Cross General Hospital, Harbin, China.
Transl Cancer Res. 2022 Feb;11(2):414-425. doi: 10.21037/tcr-21-2915.
Tripartite motif-containing protein 44 () was recently identified as a novel oncogene that is overexpressed in several types of human cancers. However, the biological functions of in epithelial ovarian cancer (EOC) remain unclear. Here, we aimed to investigate the role of in EOC and its clinical implications.
was knocked down using shRNA transfection. In vitro proliferation, invasion, migration and apoptosis of ovarian cancer (OC) cells were detected by CCK8, colony formation assay, Transwell inserts and flow cytometry analysis. The growth ability of xenograft tumors was examined in a nude mouse metastatic tumor model. Finally, we performed gene chip analysis and ingenuity pathway analysis (IPA) to analyze the potential gene network.
High expression of was observed in EOC tissues. Knockdown of TRIM44 expression substantially suppressed the proliferation, migration, invasion and colony-forming ability of EOC cells and attenuated tumor growth . Mechanistic studies revealed that silencing dramatically downregulated the expression of , , , and in EOC cells, at least in part through inactivation of the signaling pathway.
Collectively, these data suggest that downregulation of TRIM44 inhibits the progression of EOC through suppression of the signaling pathway. These results provide novel insight into the role of in tumorigenesis and suggest that it could be a potential therapeutic target for ovarian carcinoma.
含三联基序蛋白44(TRIM44)最近被鉴定为一种新型致癌基因,在多种人类癌症中过表达。然而,TRIM44在上皮性卵巢癌(EOC)中的生物学功能仍不清楚。在此,我们旨在研究TRIM44在EOC中的作用及其临床意义。
使用shRNA转染敲低TRIM44。通过CCK8、集落形成试验、Transwell小室和流式细胞术分析检测卵巢癌(OC)细胞的体外增殖、侵袭、迁移和凋亡。在裸鼠转移瘤模型中检测异种移植瘤的生长能力。最后,我们进行基因芯片分析和 Ingenuity 通路分析(IPA)以分析潜在的基因网络。
在EOC组织中观察到TRIM44高表达。敲低TRIM44表达可显著抑制EOC细胞的增殖、迁移、侵袭和集落形成能力,并减弱肿瘤生长。机制研究表明,沉默TRIM44至少部分通过使PI3K/Akt信号通路失活,显著下调EOC细胞中PI3K、AKT、mTOR、p70S6K和4EBP1的表达。
总体而言,这些数据表明TRIM44的下调通过抑制PI3K/Akt信号通路抑制EOC的进展。这些结果为TRIM44在肿瘤发生中的作用提供了新的见解,并表明它可能是卵巢癌的潜在治疗靶点。