Shanghai Key Laboratory of Female Reproductive Endocrine-Related Disease, Fudan University, Shanghai, People's Republic of China.
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People's Republic of China.
J Cell Biochem. 2019 Oct;120(10):17345-17353. doi: 10.1002/jcb.28998. Epub 2019 Jun 18.
Cervical cancer is one of the leading killers for female worldwide. Nevertheless, the less knowledge of molecular mechanism for cervical cancer limited the improvement of treatment effects. High-mobility group box 2 (HMGB2) belongs to the HMGB family, which could play diverse roles in cell proliferation. This work mainly aimed to study the functions of HMGB2 on cervical cancer cells proliferation. HMGB2 was highly expressed in cervical cancer tissue. The results of real-time polymerase chain reaction and Western blot analysis showed that HMGB2 was expressed in all the five cervical cancer cells (HeLa, CaSki, SiHa, C-33A, and C4-1 cells). In addition, HMGB2 overexpression obviously improved cell viability and promoted cell cycle progression, which suggested that HMGB2 could promote proliferation of cervical cancer cells. Moreover, HMGB2 overexpression increased the level of p-AKT and reduced the levels of p21 and p27. However, HMGB2 downregulation had contrary influences on cell proliferation, cell cycle distribution and the levels of p-AKT, p21, and p27. Notably, LY294002, as an inhibitor of AKT signaling pathway, could significantly weaken the effects of HMGB2 overexpression, which indicated that HMGB2 might promote cell proliferation by activating AKT signaling pathway. Therefore, HMGB2 was hopeful to be a candidate as a new biomarker and therapy target for cervical cancer.
宫颈癌是全球女性的主要杀手之一。然而,由于对宫颈癌分子机制的了解较少,限制了治疗效果的提高。高迁移率族蛋白 B2(HMGB2)属于 HMGB 家族,可在细胞增殖中发挥多种作用。本工作主要旨在研究 HMGB2 对宫颈癌细胞增殖的功能。HMGB2 在宫颈癌组织中高表达。实时聚合酶链反应和 Western blot 分析结果表明,HMGB2 在所有五种宫颈癌细胞(HeLa、CaSki、SiHa、C-33A 和 C4-1 细胞)中均有表达。此外,HMGB2 的过表达明显提高了细胞活力并促进了细胞周期进程,这表明 HMGB2 可促进宫颈癌细胞的增殖。此外,HMGB2 的过表达增加了 p-AKT 的水平,降低了 p21 和 p27 的水平。然而,HMGB2 的下调对细胞增殖、细胞周期分布以及 p-AKT、p21 和 p27 的水平有相反的影响。值得注意的是,LY294002 作为 AKT 信号通路的抑制剂,可显著削弱 HMGB2 过表达的作用,这表明 HMGB2 可能通过激活 AKT 信号通路促进细胞增殖。因此,HMGB2 有望成为宫颈癌的新生物标志物和治疗靶标。