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High mobility group box 3 promotes cervical cancer proliferation by regulating Wnt/β-catenin pathway

Journal of Gynecologic Oncology 2020년 31권 6호 p.91 ~ 91
Zhuang Shichao, Yu Xiaohui, Lu Ming, Li Yujiao, Ding Ning, Ding Yumei,
소속 상세정보
 ( Zhuang Shichao ) - ZIBO Central Hospital Department of Gynaecology
 ( Yu Xiaohui ) - ZIBO Central Hospital Department of Gynaecology
 ( Lu Ming ) - ZIBO Central Hospital Department of Gynaecology
 ( Li Yujiao ) - ZIBO Central Hospital Department of Gynaecology
 ( Ding Ning ) - ZIBO Central Hospital Department of Gynaecology
 ( Ding Yumei ) - ZIBO Central Hospital Department of Gynaecology

Abstract


Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

키워드

HMGB3 Protein; Cell Proliferation; beta Catenin; Cervical Cancer; shRNA

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