Clinical Significance of HMGB1 Expression in Human Gastric Cancer

Zhang, J; Zhang, R; Lu, WW; Zhu, Jian; Xia, Lei; Lǚ, Yingying; Chen, N W

doi:10.1177/039463201402700410

Cited by 16 publications

(14 citation statements)

References 24 publications

(31 reference statements)

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“…Additionally, HMGB proteins are subdivided into HMGB1, HMGB2, and HMGB3, all of which contain two HMG-box domains and a highly acidic Cterminal tail [10,11]. The current study found the expression levels of HMGB1 gene were significantly higher than that of the corresponding normal tissues in a variety of tumor tissues, including colorectal cancer, breast cancer, pancreatic cancer, melanoma, et al, which suggested that HMGB1 was involved in the occurrence and development of tumors [12][13][14][15][16]. Dong found that knockdown of the HMGB1 expression inhibited tumor growth and metastasis in human liver cancer through AKT-mediated regulation of Ki-67 and MMP-2 expression [17].…”

Section: Introductionsupporting

confidence: 48%

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Zhang

Wang

et al. 2015

Tumor Biol.

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Non-small cell lung cancer is commonly seen with higher morbidity and mortality. High-mobility group protein 1 (HMGB1) is a highly conserved nuclear protein, which is involved in multiple human diseases including cancers. However, the mechanisms of HMGB1 in non-small cell lung cancer remain unclear. The goal of the present study is to identify the relationship between HMGB1 and the progresssion of non-small cell lung cancer and investigate the molecular mechanism of HMGB1 in non-small lung cancer cell lines. Firstly, we detected the expression levels of HMGB1 by by real-time PCR and western blotting analysis, and the results demonstrated that HMGB1 was much higher expressed in non-small cell lung cancer cell lines, including A549, SPC-1-1, NCI-2170, SK-MES-1, and NCI-H1299, compared with that of WI-38. Next, 5 μM of adriamycin (AMD), 20 μM of cisplatin (DDP), and 50 μM of methotrexate (MTX) were used to treat A549 cells and SPC-A-1 cells for 48 h. The results showed that treatment with chemotherapy drugs significantly increased the levels of HMGB1 in A549 cells and SPC-A-1 cells. Moreover, the expression levels of HMGB1 increased in a time-dependent manner being treated with DDP. Then, the endogenous HMGB1 expression was successfully interferred with shRNA specific to HMGB1 in A549 and SPC-A-1 cells, which was detected by western blotting analysis. Then, the cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells were treated with increasing concentrations of cisplatin for 24, 48, and 72 h; cell viability were analyzed by MTT assay; and IC50 values were calculated. The results demonstrated that the expression level of HMGB1 in A549/DDP cells was much higher than that of A549 cells; moreover, transfection with HMGB1 shRNA in A549/DDP cells decreased the IC50 value of cisplatin in A549/DDP cells. The expression levels of autophagy-related proteins beclin-1 and LC3-II were significantly higher in A549/DDP cells or the A549 cells treated with chemotherapeutic drugs, compared with that in A549 cells. However, interference with endogenous HMGB1 obviously suppressed autophagy-related proteins and increased cell apoptosis rate and the expression of cleaved caspase-3 in A549/DDP cells. All of the data suggested that interference with the endogenous HMGB1 significantly inhibited cell autophagy and increased cell apoptosis of A549/DDP cells. Thus, the study on the resistance of chemotherapy drugs would provide a theoretical reference for clinical treatment of non-small cell lung cancer.

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Section: Introductionsupporting

confidence: 48%

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Zhang

Wang

et al. 2015

Tumor Biol.

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“…HMGB1, a highly conserved DNA-binding protein, was found to be a direct and functional downstream target of miR-665 in RB. HMGB1 is located on chromosome 8q22 and has been found to be upregulated in various human malignancies, including endometrial carcinoma, 38 gastric cancer, 39 hepatocellular carcinoma, 40 and renal cell carcinoma. 41 It is also highly expressed in RB, and its overexpression is closely associated with poor tumor differentiation and optic nerve invasion.…”

Section: Discussionmentioning

confidence: 99%

<p>MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway</p>

Wang

et al. 2019

CMAR

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Purpose: Previous studies have revealed that microRNA-665 (miR-665) is dysregulated in a variety of human cancers. However, little is known regarding its expression profiles and functions in retinoblastoma (RB). Therefore, the aims of our study were to evaluate miR-665 expression in RB and determine the precise roles of miR-665 in the progression of RB. Patients and methods: Herein, RT-qPCR was used to determine miR-665 expression levels in RB tissues and cell lines, and a series of functional experiments were performed to explore the influence of miR-665 on RB cell proliferation, colony formation, apoptosis, migration, and invasion as well as tumor growth. The molecular mechanisms underlying the tumor-suppressive action of miR-665 in RB were also explored. Results: We found that miR-665 was markedly reduced in RB tissues and cell lines and that lower miR-665 expression was strongly associated with tumor size, TNM stage, and differentiation in patients with RB. Exogenous expression of miR-665 suppressed cell proliferation, colony formation, migration, and invasion, and induced cell apoptosis in RB cells, while silencing miR-665 expression had the opposite effects. In addition, upregulation of miR-665 decreased the tumor growth of RB cells in vivo. High-mobility group box 1 (HMGB1) was identified as a direct target of miR-665 in RB cells, and decreasing the expression of HMGB1 simulated the regulatory effects of miR-665 overexpression in RB cells, while knockdown of HMGB1 expression counteracted the miR-665-mediated antitumor effects in RB cells. Moreover, miR-665 was shown to regulate the Wnt/β-catenin signaling pathway by targeting HMGB1 in vitro and in vivo. Conclusion: Taken together, our in vitro and in vivo results suggest that miR-665 acts as a tumor-suppressive miRNA in RB by directly targeting HMGB1 and inactivating the Wnt/βcatenin pathway. Hence, this miRNA is a candidate prognostic biomarker and therapeutic target in patients with RB.

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“…18 studies met our inclusion criteria and were finally included for the analysis, involving 11 different tumor types (3 studies of gastric cancer [14–16], 4 of colorectal cancer [17–20], 2 of hepatocellular carcinoma [21, 22], 2 of pancreatic cancer [23, 24], 1 of nasopharyngeal carcinoma [25], 1 of head and neck squamous-cell carcinoma [26], 1 of esophageal cancer [27], 1 of malignant pleural mesothelioma [28], 1 of bladder cancer [29], 1 of prostate cancer [30], and 1 of cervical carcinoma [31]) (Figure 1). A total of 2249 participants were analyzed for the association between HMGB1 expression and disease prognosis, of which 2090 (92.9%) and 1247 (55.4%) ones were respectively included into overall survival (OS) and progression-free survival (PFS) analyses.…”

Section: Resultsmentioning

confidence: 99%

HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review

et al. 2016

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As there are millions of cancer deaths every year, it is of great value to identify applicable prognostic biomarkers. As an important alarm, the prognostic role of high mobility group box 1 (HMGB1) in cancer remains controversial. We aim to assess the association of HMGB1 expression with prognosis in cancer patients. Systematic literature searches of PubMed, Embase and Web of Science databases were performed for eligible studies of HMGB1 as prognostic factor in cancer. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the influence of HMGB1 expression on overall survival (OS) and progression-free survival (PFS) in cancer patients. 18 studies involving 11 different tumor types were included in meta-analysis. HMGB1 overexpression was significantly associated with poorer OS (HR: 1.99; 95% CI, 1.71-2.31) and PFS (HR: 2.26; 95% CI, 1.65-3.10) irrespective of cancer types including gastric cancer, colorectal cancer, hepatocellular carcinoma, pancreatic cancer, nasopharyngeal carcinoma, head and neck squamous-cell carcinoma, esophageal cancer, malignant pleural mesothelioma, bladder cancer, prostate cancer, and cervical carcinoma. Subgroup analyses indicated geographical area and size of studies did not affect the prognostic effects of HMGB1 for OS. Morever, HMGB1 overexpression had a consistent correlation with poorer OS when detected by immunohistochemistry in tissues and enzyme-linked immunosorbent assay in serum, whereas the correlation did not exist by quantitative real-time reverse-transcription polymerase chain reaction in tissues. HMGB1 overexpression is associated with poorer prognosis in patients with various types of cancer, suggesting that it is a prognostic factor and potential biomarker for survival in cancer.

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Clinical Significance of HMGB1 Expression in Human Gastric Cancer

Cited by 16 publications

References 24 publications

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

<p>MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway</p>

HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review

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Clinical Significance of HMGB1 Expression in Human Gastric Cancer

Cited by 16 publications

References 24 publications

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

Interference with HMGB1 increases the sensitivity to chemotherapy drugs by inhibiting HMGB1-mediated cell autophagy and inducing cell apoptosis

<p>MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/&beta;-catenin pathway</p>

HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review

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<p>MicroRNA-665 inhibits the oncogenicity of retinoblastoma by directly targeting high-mobility group box 1 and inactivating the Wnt/β-catenin pathway</p>