Department of Obstetrics and Gynecology, Suzhou Municipal Hospital, No. 16, Baita West Road, Gusu District, Suzhou, 215000, Jiangsu, China.
Hum Cell. 2021 Nov;34(6):1888-1898. doi: 10.1007/s13577-021-00603-2. Epub 2021 Sep 3.
Cervical cancer is one of the leading female malignancy tumors worldwide. Structural maintenance of chromosomes 4 (SMC4), a member of the SMC family, is associated with cancer pathogenesis and progression. However, the role of SMC4 in cervical cancer is still unclear. In the study, SMC4 was increased in cervical cancer tissues compared with adjacent normal tissues. The SMC4 knockdown and overexpression were performed in cervical cancer cells. SMC4 knockdown inhibited cell proliferation, colony formation, cell migration and invasion, and suppressed epithelial-mesenchymal transition (EMT). Conversely, SMC4 overexpression exerted opposite effects. Moreover, SMC4 knockdown down-regulated stem cell markers, reduced the capacity of spheroid formation and inactivated NF-κB pathway. SMC4 overexpression contributed to stem cell markers, and stimulated spheroid formation and NF-κB pathway activation. Additionally, BAY11-7082 (an NF-κB inhibitor) alleviated the SMC4-mediated the effects in cervical cancer cells. In conclusion, these findings demonstrated that SMC4 overexpression facilitated the development of cervical cancer cells by activating NF-κBpathway, which provides a new therapeutic target for patients with cervical cancer.
宫颈癌是全球女性恶性肿瘤的主要肿瘤之一。结构维持染色体 4（SMC4）是 SMC 家族的成员，与癌症的发病机制和进展有关。然而，SMC4 在宫颈癌中的作用尚不清楚。在这项研究中，与相邻正常组织相比，SMC4 在宫颈癌组织中增加。在宫颈癌细胞中进行了 SMC4 敲低和过表达。SMC4 敲低抑制细胞增殖、集落形成、细胞迁移和侵袭，并抑制上皮-间充质转化（EMT）。相反，SMC4 的过表达则产生相反的效果。此外，SMC4 敲低下调干细胞标志物，降低球体形成能力并使 NF-κB 通路失活。SMC4 的过表达有助于干细胞标志物，并刺激球体形成和 NF-κB 通路的激活。此外，BAY11-7082（NF-κB 抑制剂）减轻了 SMC4 在宫颈癌细胞中的介导作用。总之，这些发现表明 SMC4 的过表达通过激活 NF-κB 通路促进了宫颈癌细胞的发展，为宫颈癌患者提供了一个新的治疗靶点。
