Wei Siyu, Liu Yuying, Wang Zhihao, Wei Ti, Zhou Wenkai, Li Wanwan, Zhang Jiaxin, Liu Zhiyi, Liu Zhao
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Institute of Digestive Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China.
J Cell Mol Med. 2025 Jan;29(2):e70394. doi: 10.1111/jcmm.70394.
Human L35a ribosomal protein (RPL35A) has been reported to confer higher drug resistance and viability to triple-negative breast cancer (TNBC) cells, but the mechanism related to its promotion of TNBC malignant progression is still unclear. Here, we found that silencing of RPL35A could inhibit the proliferation of TNBC cells by suppressing the G1/S phase transition. Furthermore, SMAD-specific E3 ubiquitin protein ligase 2 (Smurf2) was found to be a potential upstream ubiquitin ligase of RPL35A. Smurf2 could interact with RPL35A and promote its degradation and K63-linked polyubiquitination, thereby suppressing the G1/S phase transition and proliferation of TNBC cells. In addition, the roles of Smurf2 were confirmed in a xenograft mouse model. Finally, we found a negative correlation between the protein levels of RPL35A and Smurf2 in human TNBC tissues. In summary, Smurf2 inhibits the proliferation of TNBC cells by blocking the cell cycle process, which is associated with regulating RPL35A.
据报道，人类核糖体蛋白L35a（RPL35A）赋予三阴性乳腺癌（TNBC）细胞更高的耐药性和活力，但其促进TNBC恶性进展的机制仍不清楚。在此，我们发现沉默RPL35A可通过抑制G1/S期转换来抑制TNBC细胞的增殖。此外，SMAD特异性E3泛素蛋白连接酶2（Smurf2）被发现是RPL35A潜在的上游泛素连接酶。Smurf2可与RPL35A相互作用，促进其降解和K63连接的多聚泛素化，从而抑制TNBC细胞的G1/S期转换和增殖。此外，在异种移植小鼠模型中证实了Smurf2的作用。最后，我们发现人类TNBC组织中RPL35A和Smurf2的蛋白水平呈负相关。总之，Smurf2通过阻断细胞周期进程抑制TNBC细胞的增殖，这与调节RPL35A有关。
