HMGB1 genetic polymorphisms are biomarkers for the development and progression of breast cancer

Huang, Bifei; Tzeng, Huey En; Chen, Po Chun; Wang, Chao Qun; Su, Chen; Wang, Yan; Hu, Guoqing; Zhao, Yong; Wang, Qian; Tang, Chih Hsin

doi:10.7150/ijms.23462

Cited by 30 publications

(27 citation statements)

References 34 publications

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“…Certain SNPs influence susceptibility to breast cancer [7]. The risk of breast cancer is higher in those carrying the BRCA1 and BRCA2 gene mutations [8,9] and genetic polymorphisms such as high-mobility group box protein 1 (HMGB1) and fascin-1 (FSCN1) [10,11].…”

Section: Ivyspringmentioning

confidence: 99%

Impacts of RETN genetic polymorphism on breast cancer development

et al. 2020

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The adipokine resistin is linked with obesity, inflammation and various cancers, including breast cancer. This study sought to determine whether certain polymorphisms in the gene encoding resistin, RETN, increase the risk of breast cancer susceptibility. We analyzed levels of resistin expression in breast cancer tissue and samples from The Cancer Genome Atlas database. We also examined associations between four RETN single nucleotide polymorphisms (SNPs; rs3745367, rs7408174, rs1862513 and rs3219175) and breast cancer susceptibility in 515 patients with breast cancer and 541 healthy women without cancer. Compared with wild-type (GG) carriers, those carrying the AG genotype of the RETN SNP rs3219175 and those carrying at least one A allele in the SNP rs3219175 had a higher chance of developing breast cancer (adjusted odds ratio, AOR: 1.295, 95% confidence intervals, CI: 1.065-1.575 and 2.202, 1.701-2.243, respectively). When clinical aspects and the RETN SNP rs7408174 were examined in the breast cancer cohort, the CT genotype was linked to late-stage disease, while women with luminal A disease and at least one C allele were likely to progress to stage III/IV disease and to develop highly pathological grade III disease. Moreover, resistin-positive individuals were at greater risk than resistin-negative individuals for developing pathological grade III disease (OR: 5.020; 95% CI: 1.380-18.259). This study details risk associations between resistin and RETN SNPs in breast cancer susceptibility in Chinese Han women.

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Section: Ivyspringmentioning

confidence: 99%

Impacts of RETN genetic polymorphism on breast cancer development

et al. 2020

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“…10) Recently, many reports have showed that overexpression of extracellular HMGB1 contributed to cancer carcinogenesis and metastasis by promoting apoptotic evasion, mediating tumor-associated inflammation, and increasing tumor cell proliferation, migration and angiogenesis. 16,20,34) Enhanced HMGB1 expression were demonstrated in patients with cancers such as breast cancer, 35) cervical carcinoma, 36) metastatic prostate cancer, 37) and hepatocellular carcinoma. 38) Therefore, antagonizing HMGB1 may be a new target for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

“…19) Considering its role as mediator to the progression of tumorigenesis, HMGB1 targeted therapy may be of meaningful value in anti-cancer treatment. 20,21) Given the importance of HMGB1 in tumor initiation and progression, the aim of this study is to investigate whether triptolide could suppress growth of breast cancer by inhibiting HMGB1 expression.…”

Section: Introductionmentioning

confidence: 99%

Triptolide Suppresses Growth of Breast Cancer by Targeting HMGB1 in Vitro and in Vivo

Jiang

Chen

Xiao

et al. 2019

Biological & Pharmaceutical Bulletin

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Triptolide has been indicated potent anti-cancer effect involving multiple molecular targets and signaling pathways. High-mobility group box 1 (HMGB1) is a highly conserved DNA-binding protein taking part in breast cancer development. The therapeutic effect of triptolide on HMGB1 has not been reported. Thus, our study aims to clarify the role of HMGB1 in triptolide-induced anti-growth effect on breast cancer in vitro and in vivo. We demonstrated that triptolide significantly suppressed growth of breast cancer cells by inhibition of cell viability, clonogenic ability. Further studies evidenced that triptolide treatment not only inhibited HMGB1 mRNA expression, but also decreased supernatant level of HMGB1 in vitro. In line with these observations, exogenous recombinant HMGB1 (rHMGB1) promoted cell proliferation of breast cancer, and triptolide reversed the rHMGB1-promoted proliferative effect. As well, triptolide enhanced the antiproliferative activity of ethyl pyruvate (EP) (HMGB1 inhibitor). Furthermore, downstream correlation factors (Toll-like receptor 4 (TLR4) and phosphorylated-nuclear factor-kappaB (NF-κB) p65) of HMGB1 were significantly decreased in vitro after triptolide treatment. Consistantly, we confirmed that tumor growth was significantly inhibited after triptolide treatment in vivo. Meanwhile, immunohistochemical analyses showed that triptolide treatment significantly decreased the level of cytoplasmic HMGB1 and TLR4 expression, whereas the expression of NF-κB p65 was relatively higher in cytoplasm, and conversely lower in nucleus as compared to the control group. Collectively, these results demonstrate that triptolide suppresses the growth of breast cancer cells via reduction of HMGB1 expression in vitro and in vivo, which may provide new insights into the treament of breast cancer.

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“…The SNP rs1412125 of HMGB1 was selected because the rs1412125 polymorphism was suggested to be associated with pneumonia susceptibility, severity, and inflammatory response [ 42 ]. For HMGB1 rs1360485, patients with one C allele in the rs1360485 domain were suggested to be at greater risk of developing T2 tumors and lymph node metastasis in breast cancer [ 27 ]. The SNP rs1045411 of HMGB1 was selected because it was observed that rs1045411 was correlated with a significant effect on HMGB1 expression, and was significantly associated with clinical outcomes, especially in Chinese gastric cancer patients with aggressive status after surgery [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, HMGB1 was suggested as a novel target for potential therapeutics since highly expressed HMGB1 was found to be associated with the epithelial-to-mesenchymal transition (EMT) and the overexpression of MMP-1, MMP-3, and MMP-10 via the RAGE/NF-κB signaling pathways, facilitating prostate cancer metastasis [ 1 , 16 , 17 , 18 , 19 , 20 ]. Furthermore, polymorphisms of HMGB1 have been associated with many cancers, including oral squamous cell carcinoma (OSCC) [ 21 , 22 ], lung cancer [ 23 , 24 , 25 , 26 ], breast cancer [ 27 , 28 , 29 ], gastric cancer [ 30 ], hepatocellular carcinoma (HCC) [ 31 , 32 ], and colorectal cancer (CRC) [ 33 ], and it was suggested that the SNPs of HMGB1 may provide a potential biomarker for predicting cancer risk, tumor development, or chemotherapy responses [ 21 , 25 , 27 , 31 ]. However, the impact of HMGB1 polymorphisms on prostate cancer susceptibility and clinicopathologic characteristics has remained uninvestigated.…”

Section: Introductionmentioning

confidence: 99%

The Impact of HMGB1 Polymorphisms on Prostate Cancer Progression and Clinicopathological Characteristics

Chou

Yang

Lin

et al. 2020

IJERPH

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Prostate cancer is one of the major cancers of the genitourinary tract. High-mobility group box 1 (HMGB1) was suggested as a promising therapeutic target for prostate cancer. In this study, we aim to elucidate the associations of HMGB1 single nucleotide polymorphisms (SNPs) with prostate cancer susceptibility and clinicopathological characteristics. The HMGB1 SNPs rs1412125, rs2249825, rs1045411, and rs1360485 in 579 prostate cancer patients and 579 cancer-free controls were analyzed with real-time polymerase chain reactions (real-time PCR). All of the data were evaluated with SAS statistical software. Our results showed that the HMGB1 rs1045411 T allele genotype was significantly associated with advanced pathologic T stage (odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.021–2.012; p = 0.037) and pathologic N1 stage (OR = 2.091, 95% CI = 1.160–3.767; p = 0.012), and the rs1360485 polymorphic CT + TT genotype was associated with pathologic Gleason grade group (4 + 5) (OR = 1.583, 95% CI = 1.017–2.462; p = 0.041), pathologic T stage (3 + 4) (OR = 1.482, 95% CI = 1.061–2.070; p = 0.021), and pathologic N1 stage (OR = 2.131, 95% CI = 1.178–3.852; p = 0.011) compared with their wild-type carriers. In conclusion, our results revealed that the HMGB1 SNPs were associated with the clinical status of prostate cancer. The HMGB1 SNPs may have the potential to predict prostate cancer disease progression.

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HMGB1 genetic polymorphisms are biomarkers for the development and progression of breast cancer

Cited by 30 publications

References 34 publications

Impacts of RETN genetic polymorphism on breast cancer development

Impacts of RETN genetic polymorphism on breast cancer development

Triptolide Suppresses Growth of Breast Cancer by Targeting HMGB1 <i>in Vitro</i> and <i>in Vivo</i>

The Impact of HMGB1 Polymorphisms on Prostate Cancer Progression and Clinicopathological Characteristics

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