Second Department of Orthopedics, Beijing Daxing District People's Hospital, Beijing, China.
Department of Orthopedics, Aerospace Central Hospital, Beijing, China.
Cancer Rep (Hoboken). 2024 Aug;7(8):e2159. doi: 10.1002/cnr2.2159.
Ring finger protein 135 (RNF135) is an E3 ubiquitin ligase that has been implicated in the tumorigenesis of multiple human malignancies. However, whether RNF135 plays a role in the development of human osteosarcoma (OS) remains unknown.
RNF135 expression in 20 human OS and 20 human osteochondroma specimens were evaluated by means of immunohistochemistry staining. The effects of shRNA-mediated RNF135 knockdown on human OS cell growth and apoptosis were evaluated through a panel of in vitro studies on cell proliferation, colony formation, exposure of phosphatidylserine on the cell surface, and caspase 3/7 activation. The protein levels of PI3K, AKT, and p-AKT were determined by western blot analysis.
We detected significantly higher RNF135 levels in human OS tissues than human osteochondroma tissues. In in vitro studies, shRNA-mediated RNF135 knockdown in human OS cells inhibited proliferation and induced apoptosis. In addition, RNF135 knockdown reduced PI3K and p-AKT protein levels and activated caspase 3 and 7.
These results supported that RNF135 contributes to human OS development through PI3K/AKT-dependent mechanisms. Targeting RNF135 may provide a new therapeutic approach for treating this human malignancy.
环指蛋白 135（RNF135）是一种 E3 泛素连接酶，与多种人类恶性肿瘤的发生有关。然而，RNF135 是否在人类骨肉瘤（OS）的发展中起作用尚不清楚。
通过免疫组织化学染色评估 20 个人类 OS 和 20 个人类骨软骨瘤标本中的 RNF135 表达。通过体外细胞增殖、集落形成、细胞膜上磷脂酰丝氨酸暴露和 caspase 3/7 激活研究，评估 shRNA 介导的 RNF135 敲低对人骨肉瘤细胞生长和凋亡的影响。通过 Western blot 分析测定 PI3K、AKT 和 p-AKT 的蛋白水平。
我们在人骨肉瘤组织中检测到明显高于人骨软骨瘤组织的 RNF135 水平。在体外研究中，shRNA 介导的人骨肉瘤细胞中 RNF135 敲低抑制增殖并诱导细胞凋亡。此外，RNF135 敲低降低了 PI3K 和 p-AKT 蛋白水平，并激活了 caspase 3 和 7。
这些结果表明，RNF135 通过 PI3K/AKT 依赖性机制促进人类 OS 的发展。针对 RNF135 可能为治疗这种人类恶性肿瘤提供一种新的治疗方法。
