HMGB1 knock‐down promoting tumor cells viability and arrest pro‐apoptotic proteins via Stat3/NFκB in HepG2 cells

Alduais, Salah; Alduais, Yaser; Wu, Xiaolei; Li, Haosen; Mao, Jing

doi:10.1002/biof.1456

Cited by 6 publications

(7 citation statements)

References 25 publications

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“…Mounting evidence shows that HMGB1 can promote the malignant progression of different types of cancer through the NF-κB signalling pathway 15 - 17 . To explore whether HMGB1 plays a pivotal role in the regulation of EPHB4 and NF-κB signalling pathways in OSCC cells, western blot analysis was performed and showed that HMGB1 expression was down-regulated following EPHB4 suppression in SCC9 and UM1 cells and vice versa (Figure 5 E, 5F).…”

Section: Resultsmentioning

confidence: 99%

EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway

Chen¹,

Zhang²,

Li³

et al. 2021

J. Cancer

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Background: Malignant proliferation and cervical lymphatic metastasis restrict the prognosis of oral squamous cell carcinoma (OSCC). Erythropoietin-producing human hepatocellular B4 (EPHB4) regulates a series of tumour functions involving tumourigenesis, cancer cell attachment and metastasis. However, the mechanism of EphB4 regulating the malignant progression of OSCC has not been fully elucidated. Methods: EPHB4 expression was analysed in 65 OSCC samples and adjacent noncancerous tissues through immunohistochemistry (IHC). siRNA and overexpression plasmids were transfected into OSCC cells to modify EPHB4 expression, and then, regulatory functions were explored in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry were applied to detect proteins interacting with EPHB4. Subsequently, protein stability assays and NF-κB pathway inhibition assays were used to verify the regulation of EPHB4, high-mobility group box 1 (HMGB1) and nuclear factor-κB (NF-κB) activation. Results: EPHB4 was found to be highly expressed in OSCC tissues, which was related to tumour stage and lymphatic metastasis and resulted in a poor prognosis. Cellular experiments and mouse tongue xenograft models further confirmed that high EPHB4 expression promoted the proliferation and metastasis of OSCC tumours. Mechanistically, co-IP and mass spectrometry studies indicated that EPHB4 could bind to HMGB1 and maintain HMGB1 stability. Downregulation of HMGB1 inhibited the proliferation and metastasis of OSCC cells and inhibited NF-κB phosphorylation activation but did not affect EPHB4 expression. Conclusion:This study revealed the mechanism by which EPHB4 promotes the proliferation and metastasis of OSCC by activating the HMGB1-mediated NF-κB signalling pathway, which can be exploited as a novel marker or therapeutic target to control metastasis and improve the survival rate of OSCC.

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Section: Resultsmentioning

confidence: 99%

EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway

Chen¹,

Zhang²,

Li³

et al. 2021

J. Cancer

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“…Activation of STAT3 induces tumor cell proliferation by promoting cell‐cycle progression, enhances tumor cell survival by inhibiting apoptosis, and accelerates tumor invasion and migration by promoting epithelial‐mesenchymal transition (EMT) . In addition, STAT3 is reported to mediate cancer stem cell–like property by enhancing anoikis resistance, which is related to chemoresistance and poor prognosis . However, in HCC, little is known about the clinical significance of STAT3 function, and the precise mechanisms of its activation are still unclear.…”

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confidence: 99%

“…Because STAT3 is strongly related to inflammatory responses, its activation is induced by inflammatory cytokines and chemokines. In addition, activation of nuclear factor kappa B (NF‐κB), a potent inflammation‐related transcriptional factor, is known to accelerate STAT3 activation . In contrast, gene associated with retinoid‐interferon‐induced mortality 19 (GRIM19) is known to be a strong suppressor for STAT3 activation .…”

mentioning

confidence: 99%

“…(6,7) In addition, STAT3 is reported to mediate cancer stem cell-like property by enhancing anoikis resistance, which is related to chemoresistance and poor prognosis. (8,9) However, in HCC, little is known about the clinical significance of STAT3 function, and the precise mechanisms of its activation are still unclear. Moreover, because STAT3 is essential for cell survival in normal organs, therapies targeting STAT3 are not common.…”

mentioning

confidence: 99%

“…In addition, activation of nuclear factor kappa B (NF-κB), a potent inflammation-related transcriptional factor, is known to accelerate STAT3 activation. (9) In contrast, gene associated with retinoid-interferon-induced mortality 19 (GRIM19) is known to be a strong suppressor for STAT3 activation. (10,11) It has been reported that GRIM19 expression is decreased in many malignancies, such as breast cancer, (12) colon cancer, (13) ovarian cancer, (14) and HCC, (15) which conversely induces STAT3 activation and promotes cancer progression.…”

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confidence: 99%

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OLFM4 Enhances STAT3 Activation and Promotes Tumor Progression by Inhibiting GRIM19 Expression in Human Hepatocellular Carcinoma

et al. 2019

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Olfactomedin 4 (OLFM4) induces signal transducer and activator of transcription 3 (STAT3) activation by inhibiting gene associated with retinoid‐interferon‐induced mortality 19 (GRIM19), a strong STAT3 suppressor gene; however, the mechanisms of OLFM4 for regulating GRIM19‐STAT3 cascade in hepatocellular carcinoma (HCC) remain unclear. The functions and regulations of OLFM4, GRIM19, and STAT3 activation in HCC progression were evaluated using surgical specimens collected from 111 HCC patients or 2 HCC cell lines in vitro . Moreover, the cancer stem cell–like property of OLFM4 mediated by leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5), known as an intestinal stem cell marker, was investigated. OLFM4 was increased in HCC compared with adjacent liver tissue. The multivariate analysis revealed that high OLFM4 expression was an independent factor for poor prognosis. OLFM4 expression was negatively correlated with GRIM19 expression and positively correlated with STAT3 activation in HCC, thereby increasing cell cycle progression. OLFM4 knockdown in HCC cells increased GRIM19 expression and inhibited STAT3 activation; however, after double knockdown of GRIM19 and OLFM4, STAT3 activation decreased by OLFM4 knockdown was increased again. OLFM4 knockdown increased cell apoptosis, inhibited cell proliferation, and suppressed cancer stem cell–like property in HCC cells. The incidence of hematogenous recurrence was higher in HCC patients with high OLFM4 expression, suggesting that anoikis resistance of HCC was enhanced by OLFM4. In clinical cases, LGR5 expression and CD133 expression was correlated with OLFM4 expression in HCC, leading to poor patient prognosis. In vitro , LGR5 enhanced cancer stem cell–like property by up‐regulating OLFM4 through the Wnt signaling pathway. Conclusion : OLFM4 is induced by the LGR5‐Wnt signaling pathway and is strongly associated with aggressive tumor progression and poor prognosis in HCC by regulating STAT3‐induced tumor cell proliferation and cancer stem cell–like property. Therefore, OLFM4 is a novel prognostic predictor and a potential therapeutic target for patients with HCC.

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Aucubin protects against myocardial ischemia-reperfusion injury by regulating STAT3/NF-κB/HMGB-1 pathway

Liu,

Cheng,

et al. 2024

International Journal of Cardiology

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HMGB1 knock‐down promoting tumor cells viability and arrest pro‐apoptotic proteins via Stat3/NFκB in HepG2 cells

Cited by 6 publications

References 25 publications

EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway

EPHB4 Regulates the Proliferation and Metastasis of Oral Squamous Cell Carcinoma through the HMGB1/NF-κB Signalling Pathway

OLFM4 Enhances STAT3 Activation and Promotes Tumor Progression by Inhibiting GRIM19 Expression in Human Hepatocellular Carcinoma

Aucubin protects against myocardial ischemia-reperfusion injury by regulating STAT3/NF-κB/HMGB-1 pathway

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