Bioinformatics analysis of the prognosis and biological significance of HMGB1, HMGB2, and HMGB3 in gastric cancer

Fang, Jian; Ge, Xuhui; Xu, Wenjing; Xie, Jingjing; Qin, Zhongke; Shi, Liqing; Yin, Wu; Bian, Maohong; Wang, Hao

doi:10.1002/jcp.29233

Cited by 49 publications

(34 citation statements)

References 30 publications

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“…It can bind to the chromatin in an atypical DNA structure (e.g., single-stranded DNA) and bend the DNA to increase its flexibility 23 – 25 . Unlike HMGB1 and HMGB2, HMGB3 is expressed at low levels in normal cells but often overexpressed (up to 20-fold) in cancer cells 26 . Moreover, HMGB3 is a marker of haematopoietic stem cells, and hence, HMGB3-deficient cells cannot regenerate bone marrow for a long time 27 .…”

Section: Introductionmentioning

confidence: 99%

Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis

et al. 2021

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Distant metastasis accompanied by angiogenesis is the main cause of nasopharyngeal carcinoma (NPC)-related death. Nuclear exosomes (nEXOs) are potential tumour biomarkers. High mobility group box 3 (HMGB3), a nuclear protein, is known to be overexpressed in cancers. However, its role in NPC has not been elucidated. Here, we explore for the first time the function of nEXO HMGB3 in tumour angiogenesis involved in NPC metastasis using a series of in vitro experiments with NPC cell lines and clinical specimens and in vivo experiments with tumour xenograft zebrafish angiogenesis model. We found a high expression of HMGB3 in NPC, accompanied by the formation of micronuclei, to be associated with metastasis. Furthermore, the NPC-secreted HMGB3 expression was associated with tumour angiogenesis. Moreover, HMGB3-containing nEXOs, derived from the micronuclei of NPC cells, were ingested by the human umbilical vein endothelial cells (HUVECs), and accelerated angiogenesis in vitro and in vivo. Importantly, western blotting and flow cytometry analysis showed that circulating nEXO HMGB3 positively correlated with NPC metastasis. In summary, nEXO HMGB3 can be a significant biomarker of NPC metastasis and provide a novel basis for anti-angiogenesis therapy in clinical metastasis.

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Section: Introductionmentioning

confidence: 99%

Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis

et al. 2021

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“…Six articles including 846 patients were therefore finally included for data extraction. [12][13][14][15][16][17] All the included studies analyzed the clinicopathological value of HMGB1 in GC. The detailed search strategy is shown in Figure 1.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Value of HMGB1 expression for assessing gastric cancer severity: a systematic meta-analysis

Zhou

Yang

2021

J Int Med Res

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Objective To evaluate the clinical value of high mobility group box-1 (HMGB1) expression levels in patients with gastric cancer. Methods Articles published from January 2000 to August 2022 were searched using PubMed, Google Scholar and Science Direct, Springer, Wiley and NIH to evaluate the clinicopathological significance of HMGB1 expression in gastric cancer. Results A total of 156 publications were selected, of which six studies, comprising 846 patients, met the criteria for inclusion in this study. Forest plots of clinicopathological characteristics indicated that HMGB1 expression was not associated with age (odds ratio (OR) = 1.07, 95% confidence interval (CI): 0.89–1.28), sex (OR = 0.90, 95% CI: 0.81–1.00), TNM (OR = 1.39, 95% CI: 0.82–2.37), N stage (OR = 1.42, 95% CI: 0.97–2.07), or tumor differentiation (OR = 0.96, 95% CI: 0.71–1.29), but was highly correlated with pT stage (OR = 1.56, 95% CI: 1.17–2.07). Funnel plots showed no significant publication bias in the included studies in terms of age, sex, TNM, pT stage, N stage, or tumor differentiation. Conclusion HMGB1 expression was significantly correlated with tumor pT stage, but not with age, sex, TNM stage, tumor N stage, tumor differentiation, or lymphatic metastasis in patients with GC.

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“…24 Many studies have confirmed that HMGB1 is highly expressed in various cancers and promotes the development of cancers. 25,26 Di et al reported that HMGB1 is upregulated in ESCC and modulates the proliferation and radioresistance of ESCC. 27 In our study, we observed that circLPAR3 silencing could hinder HMEB1 expression, whereas this repression could be reversed by inhibition of miR-375 or miR-433.…”

Section: Discussionmentioning

confidence: 99%

<p>Circular RNA circLPAR3 Facilitates Esophageal Squamous Cell Carcinoma Progression Through Upregulating HMGB1 via Sponging miR-375/miR-433</p>

Cheng

Jiang

Song

et al. 2020

OTT

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Background: Circular RNAs (circRNAs) are critical regulators of many diseases, including esophageal squamous cell carcinoma (ESCC). A recent study has shown that circLPAR3 is highly expressed in ESCC, but its role and mechanism in ESCC are still unclear. Methods: The expression levels of circLPAR3, microRNA-375 (miR-375), miR-433, and high-mobility group box 1 (HMGB1) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The circular characteristic and localization of circLPAR3 were identified by Ribonuclease R (RNase R) and nuclear-cytoplasmic separation assay. Also, cell proliferation was detected by cell counting kit-8 (CCK-8) and colony formation assays. Cell migration and invasion were tested by transwell assay. Moreover, Western blot (WB) analysis was used to test the levels of proliferation and metastasis-related protein, as well as the HMGB1 protein. Besides, mice xenograft models were constructed to assess the effect of circLPAR3 on ESCC tumor growth in vivo. In addition, dual-luciferase reporter and RNA pull-down assays were used to identify the mechanism of circLPAR3. Results: CircLPAR3 was upregulated in ESCC tissues and cells, and its high expression was related to the poor prognosis of ESCC patients. CircLPAR3 was a stable cyclic transcript, mainly located in the cytoplasm, and its knockdown hindered the proliferation, migration and invasion of ESCC cells and inhibited ESCC tumor growth in vivo. MiR-375/miR-433 could be sponged by circLPAR3, and their inhibitors could reverse the suppression effect of silenced circLPAR3 on ESCC progression. HMGB1 could be targeted by miR-375/miR-433, and its overexpression also could invert the inhibition effect of circLPAR3 knockdown on ESCC progression. Conclusion: CircLPAR3 might play an oncogenic role in ESCC through sponging miR-375/ miR-433 to promote HMGB1 expression, which might provide a theoretical basis for circLPAR3 to become a biomarker for ESCC therapy.

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Bioinformatics analysis of the prognosis and biological significance of HMGB1, HMGB2, and HMGB3 in gastric cancer

Cited by 49 publications

References 30 publications

Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis

Nuclear exosome HMGB3 secreted by nasopharyngeal carcinoma cells promotes tumour metastasis by inducing angiogenesis

Value of HMGB1 expression for assessing gastric cancer severity: a systematic meta-analysis

<p>Circular RNA circLPAR3 Facilitates Esophageal Squamous Cell Carcinoma Progression Through Upregulating HMGB1 via Sponging miR-375/miR-433</p>

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