TOX3 regulates the proliferation and apoptosis of colorectal cancer by downregulating RhoB via the activation of the MAPK pathway

Yang, Wei; Wu, Wei; Liang, Hailiang; Chen, Jiejing; Dong, Xiaoqiang

doi:10.1002/cbin.11802

Cited by 5 publications

(9 citation statements)

References 50 publications

(58 reference statements)

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“…High TOX3 expression was associated with high T stage, nodal invasion, and advanced tumor stage. 41 Importantly, the Sankey plot revealed a higher risk of death in the high-risk group and a correlation between molecular subtypes with poorer prognosis and a higher risk score, supporting the prognostic relevance of the Tregs-related signature. These findings are consistent with previous studies that have shown the prognostic value of molecular subtyping in OC.…”

Section: Discussionmentioning

confidence: 76%

“…40 Yang et al investigated the expression and role of TOX high mobility group box family member 3 in CRC. 41 Notably, the authors found that messenger RNA and protein expression levels of TOX3 were markedly upregulated in CRC tissues and cell lines. High TOX3 expression was associated with high T stage, nodal invasion, and advanced tumor stage.…”

Section: Discussionmentioning

confidence: 99%

“…TOX3 is a transcription factor that plays a role in regulating gene expression and cell proliferation 40 . Yang et al investigated the expression and role of TOX high mobility group box family member 3 in CRC 41 . Notably, the authors found that messenger RNA and protein expression levels of TOX3 were markedly upregulated in CRC tissues and cell lines.…”

Section: Discussionmentioning

confidence: 99%

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Integrative analysis from multi‐center studies identifies a weighted gene co‐expression network analysis‐based Tregs signature in ovarian cancer

Cao,

Liu,

et al. 2023

Environmental Toxicology

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Ovarian cancer (OC) is a malignancy associated with poor prognosis and has been linked to regulatory T cells (Tregs) in the immune microenvironment. Nevertheless, the association between Tregs‐related genes (TRGs) and OC prognosis remains incompletely understood. The xCell algorithm was used to analyze Tregs scores across multiple cohorts. Weighted gene co‐expression network analysis (WGCNA) was utilized to identify potential TRGs and molecular subtypes. Furthermore, we used nine machine learning algorithms to create risk models with prognostic indicators for patients. Reverse transcription‐quantitative polymerase chain reaction and immunofluorescence staining were used to demonstrate the immunosuppressive ability of Tregs and the expression of key TRGs in clinical samples. Our study found that higher Tregs scores were significantly correlated with poorer overall survival. Recurrent patients exhibited increased Tregs infiltration and reduced CD8+ T cell. Moreover, molecular subtyping using seven key TRGs revealed that subtype B exhibited higher enrichment of multiple oncogenic pathways and had a worse prognosis. Notably, subtype B exhibited high Tregs levels, suggesting immune suppression. In addition, we validated machine learning‐derived prognostic models across multiple platform cohorts to better distinguish patient survival and predict immunotherapy efficacy. Finally, the differential expression of key TRGs was validated using clinical samples. Our study provides novel insights into the role of Tregs in the immune microenvironment of OC. We identified potential therapeutic targets derived from Tregs (CD24, FHL2, GPM6A, HOXD8, NAP1L5, REN, and TOX3) for personalized treatment and created a machining learning‐based prognostic model for OC patients, which could be useful in clinical practice.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Integrative analysis from multi‐center studies identifies a weighted gene co‐expression network analysis‐based Tregs signature in ovarian cancer

Cao,

Liu,

et al. 2023

Environmental Toxicology

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“…These reports further confirmed that the activation of PI3K/AKT signaling might account for the anti-CRC effect of cincumol. In addition, except for PI3K/AKT signaling, there are some other important signaling pathways that was closely correlated with the progression of CRC, such as NF-κB-Nrf2 signaling 26 , Notch signaling 27 , MAPK signaling 28 , and JAK/STAT signaling 29 . We next plan to explore whether the anti-CRC activity of cincumol was related to the aberrant expression of these known signaling.…”

Section: Discussionmentioning

confidence: 99%

Cincumol prevents malignant phenotype of colorectal cancer cell line HCT116 via inhibiting PI3K/AKT signaling in vitro

Chen

Peng

et al. 2022

Acta Cir. Bras.

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Purpose: Colorectal cancer (CRC) is a common human cancer along with higher incidence and mortality, and this study aimed to identify the effect of cincumol on CRC and its potential mechanisms. Methods: CRC cell line HCT116 was used as the material. Cell proliferation was evaluated by CCK-8 assay, and cell migration was detected by scratch test and Transwell assay. TUNEL staining assay was used to evaluate cell apoptosis. The expression of target genes was detected by qualitative real-time polymerase chain reaction and western blot assays. Results: Cincumol significantly reduced the proliferative and migratory rate and enhanced apoptotic rate of HCT116 cells. Meanwhile, the elevated levels of RBUsuh, Nicd and Tace was also observed in cincumol-treated HCT116 cells. Moreover, our findings revealed that additional cincumol inhibited the expression of p-PI3K and p-AKT, suggesting the inhibition of PI3K/AKT signaling might be involved in the protective role of cincumol on the malignant phenotypes of CRC cells in vitro . Conclusions: Cincumol inhibited the malignant phenotypes of CRC cells in vitro through inactivating PI3K/AKT signaling, suggesting that cincumol might be a potential anti-CRC agent.

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“…11 Additionally, TOX3 can mediate the expression of the apoptosis-related molecule RhoB and enhance the proliferation of colorectal tumors. 12 Moreover, TOX3 can also strengthen the metastatic ability of lung cancer cells through regulating EMT and Hippo-related signaling pathways. 13 The tripartite motif containing 56 (TRIM56, an E3 ligase) is related to the degree of malignancy of liver, lung, hematological, and ovarian cancers.…”

Section: Introductionmentioning

confidence: 99%

Accumulation of TOX high mobility group box family member 3 promotes the oncogenesis and development of hepatocellular carcinoma through the MAPK signaling pathway

Peng,

Yu,

Liu

et al. 2024

MedComm

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Microvascular invasion (MVI) has been widely valued in the field of liver surgery because MVI positivity indicates poor prognosis in hepatocellular carcinoma (HCC) patients. However, the potential molecular mechanism underlying the poor prognosis of MVI‐positive HCC patients is unclear. Therefore, this study focused on identifying the key genes leading to poor prognosis in patients with a high degree of malignancy of HCC by examining the molecular signaling pathways in MVI‐positive HCC patients. Through RNA sequencing, TOX high mobility group box family member 3 (TOX3) was demonstrated to be significantly highly expressed in MVI‐positive HCC tissues, which was associated with poor prognosis. The results of in vivo and in vitro showed that TOX3 can promote the oncogenesis and development of HCC by targeting key molecules of the MAPK and EMT signaling pathways. The IP‐MS results indicated that proteasome degradation of TOX3 in HCC cells is potentially mediated by a tripartite motif containing 56 (TRIM56, an E3 ligase) in HCC cells. Inhibiting TRIM56 enhances TOX3 protein levels. Overall, our study identified TOX3 as a key gene in the MAPK and EMT signaling pathways in HCC, and its overexpression confers significant proliferation and invasiveness to tumor cells.

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TOX3 regulates the proliferation and apoptosis of colorectal cancer by downregulating RhoB via the activation of the MAPK pathway

Cited by 5 publications

References 50 publications

Integrative analysis from multi‐center studies identifies a weighted gene co‐expression network analysis‐based Tregs signature in ovarian cancer

Integrative analysis from multi‐center studies identifies a weighted gene co‐expression network analysis‐based Tregs signature in ovarian cancer

Cincumol prevents malignant phenotype of colorectal cancer cell line HCT116 via inhibiting PI3K/AKT signaling in vitro

Accumulation of TOX high mobility group box family member 3 promotes the oncogenesis and development of hepatocellular carcinoma through the MAPK signaling pathway

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