Wang Kun, Zhang Xin-Chao
Department of Orthopedics, Affiliated Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.
Exp Ther Med. 2014 Jun;7(6):1691-1695. doi: 10.3892/etm.2014.1644. Epub 2014 Mar 28.
SUMOylation is a dynamic and reversible process. Several SUMO-specific proteases (SENPs) that remove SUMO from substrates have been shown to be amplified in a subset of cancers. SENP5 is required for cell division, as well as maintaining mitochondrial morphology and function. SENP5 has been reported to be predominantly localized to the cytoplasm of oral squamous cell carcinoma (OSCC) and is associated with the differentiation of OSCC. Western blot was used to detect the protein expression of SENP5 in osteosarcoma cells and tissue. Lentivirus-mediated siRNA was used to silence the expression of SENP5. Cell cycle distribution was determined by FACS analysis. The present study showed that SENP5 is overexpressed in osteosarcoma cells. In addition, lentivirus-mediated small interfering RNA (siRNA) of SENP5 significantly inhibited cell growth and induced apoptosis in osteosarcoma cells. SENP5 inhibition suppressed the growth and colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2. Silencing the expression of SENP5 in serum-starved U2OS and Saos-2 cells induced an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression. These observations indicate that SENP5 is required for cell growth and apoptosis and may therefore be a promising drug target for antiosteosarcoma treatment.
小泛素样修饰(SUMOylation)是一个动态且可逆的过程。几种能从底物上去除SUMO的SUMO特异性蛋白酶(SENPs)已被证实在一部分癌症中存在扩增现象。细胞分裂以及维持线粒体形态和功能都需要SENP5。据报道,SENP5主要定位于口腔鳞状细胞癌(OSCC)的细胞质中,并且与OSCC的分化有关。采用蛋白质免疫印迹法检测骨肉瘤细胞和组织中SENP5的蛋白表达。利用慢病毒介导的小干扰RNA(siRNA)使SENP5的表达沉默。通过流式细胞术分析确定细胞周期分布。本研究表明,SENP5在骨肉瘤细胞中过表达。此外,慢病毒介导的SENP5小干扰RNA(siRNA)显著抑制骨肉瘤细胞的生长并诱导其凋亡。抑制SENP5可抑制两种骨肉瘤细胞系U2OS和Saos-2的生长和集落形成能力。在血清饥饿的U2OS和Saos-2细胞中沉默SENP5的表达会导致半胱天冬酶-3/-7活性增加以及细胞周期蛋白B1表达减少。这些观察结果表明,SENP5是细胞生长和凋亡所必需的,因此可能是抗骨肉瘤治疗中一个有前景的药物靶点。