High mobility group box 3 as an emerging biomarker in diagnosis and prognosis of hepatocellular carcinoma

Zheng, Wenjie; Yang, Junling; Dong, Zhizhen; Wang, Li; Miao, Fei; Wu, Wei; Yao, Dengfu; Yao, Min

doi:10.2147/cmar.s181742

Cited by 16 publications

(11 citation statements)

References 27 publications

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“…160 The concentration of serum HMGB3 is higher in HCC, lower in liver cirrhosis, chronic hepatitis, and the healthy control. 158 The positive expression rate of HMGB3 is higher in the gastric cancer than in the peritumoral tissue. 160 Clearly, HMGB family members are promising diagnostic and prognostic markers in human cancers.…”

Section: Hmgb3mentioning

confidence: 97%

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

et al. 2020

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The high mobility group box (HMGB) protein family consists of four members: HMGB1, 2, 3, and 4. They share similar amino acid sequences and identical functional regions, especially HMGB1, 2, and 3. The homology in structure may lead to similarity in function. In fact, though their targets may be different, they all possess the fundamental function of binding and distorting target DNAs. However, further research confirmed they are distributed differently in tissues and involved in various distinct physiological and pathological cellular processes, including cell proliferation, division, migration, and differentiation. Recently, the roles of HMGB family members in carcinogenesis has been widely investigated; however, systematic discussion on their functions and clinical values in malignant tumors is limited. In this review, we mainly review and summarize recent advances in knowledge of HMGB family members in terms of structure, distribution, biochemical cascades, and specific mechanisms regarding tumor progression. Importantly, the diagnostic, prognostic, and therapeutic value of these proteins in cancers is discussed. Finally, we envisage the orientation and challenges of this field in further studies.

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Section: Hmgb3mentioning

confidence: 97%

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

et al. 2020

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“…We identified a total of 18 studies (Akaike et al, ; Soldevilla et al, ; Chuangui et al, ; Chung et al, ; Cui, Cai, Ding, & Gao, ; W. He et al, ; Gao et al, ; Kwon et al, ; Liu et al, ; Ueda et al, ; Peng et al, ; Rhead et al, ; Kang, Zhang, Zeh, Lotze, & Tang, ; Takeda et al, ; Wittwer et al, ; Xiao et al, ; Yao et al, ; Zheng et al, ) from public databases (PubMed, Web of Science, EMBASE, and Cochrane). The meta‐analysis results indicated that the pooled hazard ratios (HR) were 1.90 (95% confidence interval [CI] = 1.30−2.78) for the high versus low HMGB1, HMGB2, and HMGB3 expression groups ( p < .0001; Figure a) in GC.…”

Section: Resultsmentioning

confidence: 99%

“…The HMGB2 family is 85% similar to the HMGB1 family, with different biological functions in cells (Polanská, Dobšáková, Dvořáčková, Fajkus, & Štros, ); and (c) HMGB3, a member of the high mobility subfamily of the X‐linked HMG proteins that is up to 80% homologous with HMGB1 and HMGB2 (Nemeth, ). An increasing number of studies have reported that HMGB1, HMGB2, and HMGB3 play an important role in several cancers, including hepatocellular carcinoma (Kwon et al, ; Liu et al, ; Xiao et al, ; Zheng et al, ), pancreatic cancer (Chung et al, ; Takeda et al, ; Wittwer et al, ), colon cancer (Soldevilla et al, ; Ueda et al, ; Peng et al, ; Yao et al, ), and esophageal squamous cell carcinoma (Chuangui, Peng, & Zhentao, ; Gao et al, ). However, the role of HMGB1, HMGB2, and HMGB3 expression in GC remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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

Fang

et al. 2019

Journal Cellular Physiology

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High mobility group box (HMGB) consists primarily of HMGB1, HMGB2, and HMGB3 proteins. Although abnormal HMGB expression is associated with various tumors, the relationship with gastric cancer (GC) remains unclear. In this study, HMGB1, HMGB2, and HMGB3 expression was analyzed using the Oncomine and TCGA databases. Correlations between HMGB1, HMGB2, and HMGB3 and clinicopathological factors were analyzed. cBioPortal was used to analyze HMGB1, HMGB2, and HMGB3 genetic alterations and its gene regulation network in GC tissue. HMGB1, HMGB2, and HMGB3 expression was higher in tumor tissues than in normal tissues, especially in GC. High HMGB1, HMGB2, and HMGB3 expression may predict a poor prognosis among patients with GC (hazard ratios [HR] = 1.90; 95% confidence interval [CI]: [1.30−2.78]) and human digestive system neoplasm (HR = 1.85; 95% CI [1.64−2.10]). These findings suggest that HMGB1, HMGB2, and HMGB3 may be useful prognostic indicators for patients with GC.

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“…HCC [9] and ESCC [10]. Researches also highlighted the role of HMGB3 in proliferation [11], metastasis [12], hypoxia [13] and drug resistance [14].…”

Section: Discussionmentioning

confidence: 99%

TGIF2-Induced HMGB3 Promotes Esophageal Squamous Cell Carcinoma Progression Through TGFβ Signaling

Niu

Yang

Zhou

et al. 2021

Preprint

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Background: Proliferation and metastasis are the major malignant phenotypes of esophageal squamous cell carcinoma (ESCC) and the main causes for poor survival in patients with ESCC. Nevertheless, the underlying mechanisms of ESCC proliferation and metastasis remains unclear. The high mobility group box protein family 3 (HMGB3) is one of the HMGB family members. It is critically involved in the occurrence and development of various carcinomas. However, the knowledge of HMGB3 in ESCC remains limited. In this study, we elucidated the role of HMGB3 in ESCC proliferation and metastasis, and the concrete mechanism. Methods: Expression level of HMGB3 and TGF-β interacting factor 2 (TGIF2) in ESCC cell lines and tissues was quantified by qRT-PCR, Western Blot, and immunohistochemistry. In vitro and in vivo assays revealed the functions of TGIF2 and HMGB3 in ESCC. RNA-seq was performed to search for the downstream signaling of HMGB3. ChIP assay and were performed to explore the relationship of HMGB3 and TGIF2. HMGB3-interacting protein was validated by immunoprecipitation.Results: Higher expression of TGIF2 and HMGB3 was observed in ESCC cell lines and tissues and was associated with worse prognosis of ESCC patients. TGIF2 and HMGB3 upregulation could promote ESCC proliferation and metastasis, and vice versa. TGIF2 and HMGB3 upregulation can activate Smad-dependent TGF-β signaling. TGIF2 can transcriptionally regulate HMGB3, and its TGF-β inducing capability and oncogenic role are at least partly HMGB3-dependent. Additionally, TLR3 was identified as a client protein of HMGB3, and their combination might be the reason of TGF-β activation. Conclusions: Collectively, HMGB3-dependent TGIF2 overexpression activates TGF-β signaling and promotes the proliferation and metastasis of ESCC via TLR3 regulation. These findings revealed that TGIF2 and HMGB3 could be prognostic indicators of ESCC and targeting TGIF2/HMGB3/TLR3 axis might improve the OS of ESCC patients.

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High mobility group box 3 as an emerging biomarker in diagnosis and prognosis of hepatocellular carcinoma

Cited by 16 publications

References 27 publications

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

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

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

TGIF2-Induced HMGB3 Promotes Esophageal Squamous Cell Carcinoma Progression Through TGFβ Signaling

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