Li Wenhan, Shi Ru, Gao Yumei, Wang Xiaoman, Shen Tiantian, Liu Xiaoli, Wu Qiulei, Xu Xiaohan, Wang Zanhong, Du Shi, Sun Si, Yang Lu, Cai Jing, Liu Lin
Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Obstetrics and Gynecology, Shanxi Children's Hospital, Shanxi Maternal and Child Health Hospital, Taiyuan, Shanxi, China.
J Biol Chem. 2025 Feb;301(2):108170. doi: 10.1016/j.jbc.2025.108170. Epub 2025 Jan 8.
Cervical cancer is the fourth most common malignancy and the fourth leading cause of cancer-related death among women. Advanced stages and resistance to treatment in cervical cancer induce cancer-related deaths. Although epigenetics has been known to play a vital role in tumor progression and resistance, the function of epigenetic regulators in cervical cancer is an area of investigation. In this study, we focused on an epigenetic regulator, polycomb repressor complex 1 in cervical cancer. Through bioinformatics analysis and immunochemistry, we subsequently identified chromobox 2CBX2), the deregulated subunit of polycomb repressor complex 1, which is upregulated in cervical cancer and associated with poor prognosis and unfavorable clinicopathological characteristics. We provided functional evidence demonstrating that CBX2 promoted cervical cancer cell proliferation. Furthermore, CBX2 exhibited an antiapoptotic effect, which induced resistance to cisplatin and ionizing radiation in cervical cancer cells. Moreover, CBX2 was involved in maintaining cancer stemness. These findings suggest that CBX2 plays an important role in cervical cancer progression and resistance to treatment, and may serve as a potential biomarker for prognosis and resistance as well as a potential therapeutic target.
宫颈癌是女性中第四大常见恶性肿瘤，也是癌症相关死亡的第四大主要原因。宫颈癌的晚期阶段和对治疗的耐药性会导致癌症相关死亡。尽管已知表观遗传学在肿瘤进展和耐药性中起着至关重要的作用，但表观遗传调节因子在宫颈癌中的功能仍是一个研究领域。在本研究中，我们聚焦于宫颈癌中的一种表观遗传调节因子——多梳抑制复合物1。通过生物信息学分析和免疫化学，我们随后鉴定出了多梳抑制复合物1失调的亚基染色质盒蛋白2（CBX2），其在宫颈癌中上调，与预后不良及不利的临床病理特征相关。我们提供了功能证据，证明CBX2促进宫颈癌细胞增殖。此外，CBX2表现出抗凋亡作用，可诱导宫颈癌细胞对顺铂和电离辐射产生耐药性。此外，CBX2参与维持癌症干性。这些发现表明，CBX2在宫颈癌进展和治疗耐药性中起重要作用，可能作为预后和耐药性的潜在生物标志物以及潜在的治疗靶点。
