Biological functions and theranostic potential of HMGB family members in human cancers

Niu, Liaoran; Yang, Wanli; Duan, Lili; Wang, Xiaoqian; Li, Yiding; Xu, Chengchao; Liu, Chao; Zhang, Yujie; Zhou, Wei; Liu, Jinqiang; Zhao, Qingchuan; Han, Yu; Hong, Liu; Fan, Daiming

doi:10.1177/1758835920970850

Cited by 37 publications

(42 citation statements)

References 179 publications

(341 reference statements)

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“…From the outset, we found that HMGBs were significantly upexpressed in various TCGA cancers, except that HMGB2/3 were down-expressed in LAML. Despite that the overexpression of HMGB1 in cancers was the most prevalently reported (Niu et al, 2020), we found that HMGB3 was highly expressed in the largest variety of cancers and altered most frequently. Integrating the results of two steps of survival analyses, high expression of HMGBs suggested unfavorable prognosis in the following cancers: HMGB1 in ACC; HMGB2 in ACC, KIRP, LGG, LIHC, MESO; and HMGB3 in BRCA, ESCA, SARC, and SKCM.…”

Section: Discussioncontrasting

confidence: 71%

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Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

2021

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Background: High mobility group box (HMGB) proteins are DNA chaperones involved in transcription, DNA repair, and genome stability. Extracellular HMGBs also act as cytokines to promote inflammatory and immune responses. Accumulating evidence has suggested that HMGBs are implicated in cancer pathogenesis; however, their prognostic and immunological values in pan-cancer are not completely clear.Methods: Multiple tools were applied to analyze the expression, genetic alternations, and prognostic and clinicopathological relevance of HMGB in pan-cancer. Correlations between HMGB expression and tumor immune-infiltrating cells (TIICs), immune checkpoint (ICP) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) in pan-cancer were investigated to uncover their interactions with the tumor immune microenvironment (TIME). Gene set enrichment analysis (GSEA) was conducted for correlated genes of HMGBs to expound potential mechanisms.Results: HMGB expression was significantly elevated in various cancers. Both prognostic and clinicopathological significance was observed for HMGB1 in ACC; HMGB2 in ACC, LGG, LIHC, and SKCM; and HMGB3 in ESCA. Prognostic values were also found for HMGB2 in KIRP and MESO and HMGB3 in BRCA, SARC, SKCM, OV, and LAML. The global alternation of HMGBs showed prognostic significance in ACC, KIRC, and UCEC. Furthermore, HMGBs were significantly correlated with TIIC infiltration, ICP expression, MSI, and TMB in various cancers, indicating their regulations on the TIME. Lastly, results of GSEA-illuminated genes positively correlated with HMGBs which were similarly chromosome components participating in DNA activity-associated events.Conclusion: This study demonstrated that HMGBs might be promising predictive biomarkers for the prognosis and immunotherapeutic response, also immunotherapy targets of multiple cancers.

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Section: Discussioncontrasting

confidence: 71%

“…HMGBs are predominantly in the nucleus and act as DNA chaperones, thereby modulating chromosome stabilization, telomerase maintenance, replication, transcription, and DNA repair (Cheng et al, 2020). In the cytoplasmic or extracellular milieu, HMGBs act as chemokines or cytokines to evoke inflammatory and immune responses (Niu et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

2021

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“…HMG is divided into 3 families, HMGA, HMGB, and HMGN of which the HMGB family has 4 members, namely HMGB1, HMGB2, HMGB3, and HMGB4 ( Niu et al, 2020 ). Research studies have shown that HMGB1 and HMGB2 are closely related to colorectal cancer and can be used as potential diagnostic and prognostic markers ( Cheng et al, 2020 ; Liang et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

HMGB3 is a Potential Therapeutic Target by Affecting the Migration and Proliferation of Colorectal Cancer

Gong

Guo

Yuan

et al. 2022

Front. Cell Dev. Biol.

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Colorectal cancer is one of the common malignant tumors in the digestive system, with high incidence and mortality rate. Therefore, there is an urgent need to identify and develop new molecular targets for colorectal cancer treatment. Previous studies have pointed out the important role of HMGB3 in tumors, and how it works in colorectal cancer needs to be studied in depth. In this study, we found that HMGB3 was highly expressed in COAD in the cBioPortal and GEPIA2 databases. Kaplan-Meier analysis showed that compared with patients with lower HMGB3 levels, patients with higher HMGB3 levels had poorer OS (p = 0.001). We also found a correlation between HMGB3 expression and immune infiltration of CRC. To investigate the mechanism of HMGB3 knockdown-mediated colorectal cancer inhibition, we detected a downregulation of N-cadherin, Vimentin and β-catenin proteins after knockdown of HMGB3. Taken together, HMGB3 can be an effective target for CRC treatment in the future, and we have reason to believe that HMGB3 will be of greater value in more tumors in the near future.

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“…High mobility group box 3 (HMGB3) belongs to the high mobility group protein subfamily, which also includes HMGB1, HMGB2, and HMGB4 (Reeves, 2015). HMG box family members play important roles in cancer by binding to DNA structure and multiple other patterns (Niu et al, 2020). In particular, HMGB1 plays paradoxical roles in promoting cancer cell proliferation and inhibiting malignant cell survival (Kang et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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

Zhong

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Neuroblastoma (NB) is the most common solid tumor apart from central nervous system malignancies in children aged 0–14 years, and the outcomes of high-risk patients are dismal. High mobility group box 3 (HMGB3) plays an oncogenic role in many cancers; however, its biological role in NB is still unclear. Using data mining, we found that HMGB3 expression was markedly elevated in NB patients with unfavorable prognoses. When HMGB3 expression in NB cell lines was inhibited, cell proliferation, migration, and invasion were suppressed, and HMGB3 knockdown inhibited NB tumor development in mice. RT−PCR was employed to detect mRNA expression of nine coexpressed genes in response to HMGB3 knockdown, and TPX2 was identified. Furthermore, overexpression of TPX2 reversed the cell proliferation effect of HMGB3 silencing. Multivariate Cox regression analysis indicated that HMGB3 and TPX2 might be independent prognostic factors for overall survival and event-free survival, which showed the highest significance (p < 0.001). According to the nomogram predictor constructed, the integration of gene expression and clinicopathological features exhibited better prognostic prediction power. Furthermore, the random forest algorithm and receiver operating characteristic curves also showed that HMGB3 and TPX2 played important roles in discriminating the vital status (alive/dead) of patients in the NB datasets. Our informatics analysis and biological experiments suggested that HMGB3 is correlated with the unfavorable clinical outcomes of NB, and plays an important role in promoting cell growth, proliferation, and invasion in NB, potentially representing a new therapeutic target for tumor progression.

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Biological functions and theranostic potential of HMGB family members in human cancers

Cited by 37 publications

References 179 publications

Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

HMGB3 is a Potential Therapeutic Target by Affecting the Migration and Proliferation of Colorectal Cancer

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

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