Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, PR China; Department of Obstetrics and Gynecology, The Central Hospital of Jingzhou City, Jingzhou, 434000, PR China.
Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, PR China.
Biochem Biophys Res Commun. 2020 Apr 9;524(3):683-688. doi: 10.1016/j.bbrc.2020.01.150. Epub 2020 Feb 4.
Ubiquitin-specific protease 14 (USP14) is one of the three proteasome-associated deubiquitinating enzymes and implicated in the progression of various cancers. However, the role of USP14 in ovarian cancer remains unknown. By using an unbiased qRT-PCR screen, here we show that USP14 is considerably increased in cisplatin-resistant ovarian cancer cells. Overexpression of USP14 confers resistance to cisplatin-sensitive ovarian cancer cells. Genetic or pharmacological inhibition of USP14 is able to reverse cisplatin-resistance of ovarian cancer cells, which was accompanied by decreased protein expression of BCL6. Besides, BCL6 protein level was also increased in cisplatin-resistant ovarian cancer cells and silencing of BCL6 in these cells restored their sensitivity to cisplatin. At the molecular lever, we found that USP14 interacted with BCL6 and prevented it from proteasomal-dependent degradation. Thus, our results provide a rationale to target USP14-BCL6 axis in ovarian cancer that may be therapeutically beneficial.
泛素特异性蛋白酶 14（USP14）是三种蛋白酶体相关去泛素化酶之一，与多种癌症的进展有关。然而，USP14 在卵巢癌中的作用尚不清楚。通过使用无偏 qRT-PCR 筛选，我们发现顺铂耐药卵巢癌细胞中 USP14 的表达显著增加。USP14 的过表达赋予顺铂敏感卵巢癌细胞耐药性。USP14 的遗传或药理学抑制能够逆转卵巢癌细胞的顺铂耐药性，同时伴随 BCL6 蛋白表达的降低。此外，BCL6 蛋白水平在顺铂耐药卵巢癌细胞中也增加，而这些细胞中 BCL6 的沉默恢复了它们对顺铂的敏感性。在分子水平上，我们发现 USP14 与 BCL6 相互作用，阻止其被蛋白酶体依赖的降解。因此，我们的研究结果为靶向 USP14-BCL6 轴治疗卵巢癌提供了理论依据，可能具有治疗益处。
