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

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.

LncRNA NOP14-AS1 Promotes Tongue Squamous Cell Carcinoma Progression by Targeting MicroRNA-665/HMGB3 Axis

“…HMGB3 was predicted to harbor putative binding sequences for miR-665 ( Figure 3E ) and was selected for further identification considering its critical roles during tumor genesis and development. 19–21 Next, luciferase reporter assay was performed. It was found that miR-665 mimic clearly lessened the luciferase activity of WT-HMGB3, whereas no evident suppression was identified in CAL-27 and SCC-15 cells when the binding sequences were mutated ( Figure 3F ).…”

Glaucocalyxin A Inhibits the Malignant Progression of Epithelial Ovarian Cancer by Affecting the MicroRNA-374b-5p/HMGB3/Wnt-β-Catenin Pathway Axis

“…The Wnt-β-catenin signaling pathway is closely involved in regulating pivotal cellular functions, including proliferation, differentiation, migration, and apoptosis ( 32 ). HMGB3 promotes tumor development by moderating the Wnt-β-catenin pathway ( 19 , 20 , 33 ). Our results showed that HMGB3 knockdown decreased the protein levels of Wnt3a and β-catenin in EOC cells.…”

HMGB3 is Associated With an Unfavorable Prognosis of Neuroblastoma and Promotes Tumor Progression by Mediating TPX2

“…Dysregulation of the WNT signaling pathways in carcinogenesis is observed in multiple solid and liquid tumors (Zhan et al, 2017). Studies have indicated that HMGB3 promotes cancer cell proliferation by activating the WNT/β-catenin pathway (Zhang et al, 2017;Xie et al, 2019;Zhuang et al, 2020). Gu et al (2019) discovered that HMGB3 silencing inhibited BC growth by interacting with HIF-1α.…”

“…Moreover, HMGB1 is an important paralog of HMGB3. Over the past decade, the carcinogenic effects of HMGB3 have been reported in a variety of tumors, including colorectal cancer (CRC) (Zhang et al, 2017), breast cancer (BC) (Gu et al, 2019), cervical cancer (Li Z. et al, 2020;Zhuang et al, 2020), and non-small cell lung cancer (NSCLC) . Additionally, HMGB3 depletion is suggested to reduce the cisplatin resistance of ovarian cancer cells (Mukherjee et al, 2019).…”