Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis

Wang, Chaoqun; Huang, Bifei; Wang, Yan; Tang, Chih‐Hsin; Jin, Hongchuan; Shao, Feng; Shao, Jun-Kang; Wang, Qian; Zeng, Yue

doi:10.1038/s41598-020-75783-2

Cited by 13 publications

(13 citation statements)

References 23 publications

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“…WTAP staining in colorectal tissues was practically uniform throughout all tumor cells, so we needed to only evaluate WTAP staining intensity. The intensity of nuclear staining for WTAP was assessed in CRC tissue and scored on a 4-point scale from 0 (negative) to 1 (weak), 2 (moderate), or 3 (strong) [21][22][23][24]. High WTAP expression was defined as a staining intensity of positive invasive cancer cells of 2 or 3 [22,24].…”

Section: Assessment Of Stainingmentioning

confidence: 99%

“…The intensity of nuclear staining for WTAP was assessed in CRC tissue and scored on a 4-point scale from 0 (negative) to 1 (weak), 2 (moderate), or 3 (strong) [21][22][23][24]. High WTAP expression was defined as a staining intensity of positive invasive cancer cells of 2 or 3 [22,24]. Each entire section was scanned and scored independently by two pathologists.…”

Section: Assessment Of Stainingmentioning

confidence: 99%

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Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation

et al. 2022

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Few reports exist regarding the expression and function of Wilms’ tumor 1-associated protein (WTAP) in colorectal cancer (CRC), and the evidence is controversial. Our analysis explored the expression of WTAP in CRC tissue, and analyzed its clinical and prognostic significance. WTAP expression was significantly higher in CRC tissue than in colorectal adenoma and normal colorectal tissue. WTAP was highest in left colon tumor samples and negatively associated with tumor differentiation, as well as depth of tumor invasion. In multiple logistic regression analysis, independent predictors of WTAP expression in CRC included tumor in the left colon (odds ratio = 2.634; 95% confidence interval: 1.129–6.142; P = 0.025) and poorly differentiated tissue (0.072; 0.014–0.367; P = 0.002). No clear relationship was observed between CRC patient prognosis and WTAP expression. We suggest that WTAP expression is upregulated in CRC, highly expressed in left colon cancer and negatively correlated with tumor differentiation.

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Section: Assessment Of Stainingmentioning

confidence: 99%

Section: Assessment Of Stainingmentioning

confidence: 99%

Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation

et al. 2022

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“…Moreover, a recent study showed that cytoplasmic HMGB1 expression had been associated with high-grade CRC and poor prognosis. But, there was a better survival prognosis in CRC patients with nuclear HMGB1 expression in comparison with other patients [ 13 ]. We wondered why HT29 cells infected with HSV-HMGB1 showed a different pattern of HMGB1 localization in normoxic condition.…”

Section: Discussionmentioning

confidence: 99%

“…It has also been shown that during hypoxia, nucleus-to-cytosol translocated HMGB1 binds to DNA, resulting in hepatocellular carcinoma proliferation [ 12 ]. However, in CRC and colorectal adenoma tissue samples, high rates of nuclear HMGB1 expression (84.0% and 92.6%, respectively) and moderate cytoplasmic HMGB1 expression (25.2% and 11.8%, respectively) have been reported [ 13 ]. Here, to determine whether oncolytic virotherapy and overexpression of HMGB1 under hypoxic conditions can affect subcellular localization of the protein and tumor cell death, we infected three colorectal cancer cell lines with a recombinant oHSV expressing HMGB1 and investigated its effects on the cell lines in in vitro normoxic and hypoxic environments.…”

Section: Introductionmentioning

confidence: 99%

Cell type-specific response of colon cancer tumor cell lines to oncolytic HSV-1 virotherapy in hypoxia

et al. 2022

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Background Novel strategies are required since the hypoxic tumor microenvironment is one of the important impediments for conventional cancer therapy. High mobility group box 1 (HMGB1) protein can block aerobic respiration in cancer cells. We hypothesized that HMGB1could also kill the colorectal cancer cells during hypoxia. Methods In this study, we developed oncolytic herpes simplex virus type 1 expressing HMGB1 protein (HSV-HMGB1) and investigated the cytotoxic effect of HSV-HMGB1 and its parental virus (HSV-ble) on three colorectal cancer cells (HCT116, SW480, and HT29) under normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. We further identified potential autophagy- related genes in HT29 cells by retrieving mRNA expression microarray datasets from the Gene Expression Omnibus database. These genes were then detected in HT29 cells infected with HSV-HMGB1 and HSV-ble during normoxia and hypoxia by Real-Time quantitative PCR (qRT-PCR). Results The cytotoxic effect of HSV-HMGB1 was significantly higher than that of HSV-ble during normoxia; however, during hypoxia, HSV-HMGB1 enhanced the viability of HT29 cells at MOI 0.1. Analyzing the cell death pathway revealed that HSV-HMGB1 induced autophagy in HT29 cells under hypoxic conditions. Conclusion In conclusion, it appears that oncolytic virotherapy is cell context-dependent. Therefore, understanding the cancer cells’ characteristics, microenvironment, and cell signaling are essential to improve the therapeutic strategies.

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“…Upon exposure to infectious agents or endogenous danger signals, including bacteria, viruses, endotoxin (LPS), and extracellular adenosine triphosphate (ATP), immune cells can translocate HMGB1 nuclei into the cytoplasm or even extracellularly [ 8 , 30 ]. HMGB1 with different subcellular localization possesses diverse biological functions [ 31 ]. In the present study, we demonstrated that HMGB1 level in HD-11 cells after MG infection was downregulated as MG infection progressed ( Figure 1 A,B).…”

Section: Discussionmentioning

confidence: 99%

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection

Wang

et al. 2022

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High-mobility group box 1 (HMGB1), a member of damage-associated molecular patterns (DAMPs), is involved in the immune regulation of several infectious diseases. Mycoplasma gallisepticum (MG) infection is proved to cause an abnormal immune response, but the role of HMGB1 in MG-induced chronic respiratory disease (CRD) is unclear. In this study, we found that HMGB1 was released from the nucleus to the extracellular in macrophages upon infection with MG. Extracellular HMGB1 bound to TLR2 activating the NF-κB pathway triggering a severe inflammatory storm and promoting the progression of MG infection. More importantly, TLR4 could be activated by HMGB1 to trigger immune disorders after TLR2 was silenced. This disease process could be interrupted by ethyl pyruvate (EP) inhibition of HMGB1 release or glycyrrhizic acid (GA). Furthermore, treatment of MG-infected chickens with GA significantly alleviated immune organ damage. In conclusion, we demonstrate that HMGB1 is secreted extracellularly to form an inflammatory environment upon MG infection, triggering a further cellular inflammatory storm in a positive feedback approach. Blocking MG-induced HMGB1 release or suppression downstream of the HMGB1-TLR2/TLR4 axis may be a promising novel strategy for the treatment of CRD. Furthermore, this study may provide a theoretical reference for understanding non-LPS-activated TLR4 events.

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Subcellular localization of HMGB1 in colorectal cancer impacts on tumor grade and survival prognosis

Cited by 13 publications

References 23 publications

Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation

Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation

Cell type-specific response of colon cancer tumor cell lines to oncolytic HSV-1 virotherapy in hypoxia

Extracellular HMGB1 as Inflammatory Mediator in the Progression of Mycoplasma Gallisepticum Infection

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