Department of Center for Medical Experiments, The Third Xiang-Ya Hospital of Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China.
State Key Lab of Reproductive Medicine, Nanjing Medical University, 101 Longmian Ave., Nanjing, 211166, Jiangsu, China.
Mol Med. 2020 Oct 27;26(1):96. doi: 10.1186/s10020-020-00226-7.
Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue.
We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo.
First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo.
Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.
Kelch 重复和 BTB 结构域蛋白 8(KBTBD8)已被确定为女性生育因子。然而,目前尚无关于 KBTBD8 在卵巢上皮性癌(EOC)进展中作用的报道。本研究旨在探讨这一问题。
我们首先检测了 KBTBD8 在 EOC 组织和细胞中的表达。接下来,我们进行了 RNA 测序以揭示整体机制。然后,我们研究了 KBTBD8 在培养的 EOC 细胞增殖、迁移和健康状态中的作用。最后,我们采用肿瘤异种移植模型来评估 KBTBD8 在体内的作用。
首先,KBTBD8 水平在 EOC 组织和细胞中显著升高。其次,比较 RNA 测序鉴定出 KBTBD8 可能调节的更多与肿瘤发生相关的基因。然后,我们发现 KBTBD8 敲低显著降低了 EOC 细胞的增殖、迁移和多种与肿瘤发生相关的激酶的活性。最后,KBTBD8 敲低显著抑制了体内卵巢肿瘤的形成。
适当的 KBTBD8 水平对于卵巢体细胞(如卵巢上皮细胞)的健康生长至关重要。KBTBD8 过度可能是 EOC 进展的重要推动力。KBTBD8 减少可显著抑制 EOC 的增殖和迁移。