Department of Gynaecology, ZIBO Central Hospital, Zibo, Shandong, China.
J Gynecol Oncol. 2020 Nov;31(6):e91. doi: 10.3802/jgo.2020.31.e91.
High mobility group box 3 (HMGB3) plays an important role in the development of various cancer. This study aims to explore whether HMGB3 regulates cervical cancer (CC) progression and elucidate the underlying mechanism.
HMGB3 expression in clinical patients' tumor samples were determined by real-time quantitative polymerase chain reaction (qRT-PCR) and western blot. HMGB3 overexpression/knockdown were used to investigate its function. Cell apoptosis and cycle were detected by Annexin V/PI staining and flow cytometry. In vivo tumor model was made by subcutaneous injection of HeLa cells transfected with shRNAs targeting HMGB3 (sh-HMGB31) into the flank area of nude mice. Western blot was used to detect the levels of β-catenin, c-Myc, and matrix metalloproteinase-7 (MMP-7) in Hela and CaSki cells transfected with sh-HMGB3 or shRNAs targeting β-catenin.
Both messenger RNA and protein levels of HMGB3 were upregulated in CC tissues from patients. High expression level of HMGB3 had positive correlation with serosal invasion, lymph metastasis, and tumor sizes in CC patient. Functional experiments showed that HMGB3 could promote CC cell proliferation both in vitro and in vivo. The expression levels of c-Myc and MMP-7 were increased, resulting in regulating cell apoptosis, cell cycle, and activating Wnt/β-catenin pathway.
Our data indicated that HMGB3 may serve as an oncoprotein. It could be used as a potential prognostic marker and represent a promising therapeutic strategy for CC treatment.
高迁移率族蛋白 B3（HMGB3）在多种癌症的发展中起着重要作用。本研究旨在探讨 HMGB3 是否调节宫颈癌（CC）的进展，并阐明其潜在机制。
通过实时定量聚合酶链反应（qRT-PCR）和蛋白质印迹法测定临床患者肿瘤样本中的 HMGB3 表达。使用 HMGB3 过表达/敲低来研究其功能。通过 Annexin V/PI 染色和流式细胞术检测细胞凋亡和细胞周期。通过将靶向 HMGB3 的 shRNA（sh-HMGB31）转染的 HeLa 细胞皮下注射到裸鼠的侧腹区域来建立体内肿瘤模型。使用蛋白质印迹法检测转染 sh-HMGB3 或靶向β-连环蛋白的 shRNA 的 Hela 和 CaSki 细胞中β-连环蛋白、c-Myc 和基质金属蛋白酶-7（MMP-7）的水平。
HMGB3 的信使 RNA 和蛋白水平在 CC 患者的组织中均上调。HMGB3 的高表达水平与 CC 患者的浆膜侵犯、淋巴转移和肿瘤大小呈正相关。功能实验表明，HMGB3 可以在体外和体内促进 CC 细胞的增殖。c-Myc 和 MMP-7 的表达水平增加，导致调节细胞凋亡、细胞周期，并激活 Wnt/β-连环蛋白通路。
我们的数据表明 HMGB3 可能作为一种癌蛋白发挥作用。它可以作为一种潜在的预后标志物，并代表 CC 治疗的一种有前途的治疗策略。
