miR-34a induces immunosuppression in colorectal carcinoma through modulating a SIRT1/NF-κB/B7-H3/TNF-α axis

Fang, Meng; Yang, Man; Chen, Yinshuang; Chen, Weichang; Wang, Weipeng

doi:10.1007/s00262-021-02862-2

Cited by 26 publications

(16 citation statements)

References 48 publications

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“…Given that osteopontin is an extracellular matrix protein secreted by both tumor cells and non-tumor stromal cells, it is likely that the observable effects of SIRT1 on EMT are associated with the tumor microenvironment. More recently, in studying colorectal carcinoma, Meng et al ( 37 ) presented results that demonstrated alterations in the SIRT1/NF-κB/B7-H3/TNF-α signaling axis, suggesting that the protein level of B7-H3 is downregulated via SIRT1-mediated NF-κB deactivation. However, whether a negative feedback cycle exists between B7-H3 and SIRT1 requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway

et al. 2022

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Section: Discussionmentioning

confidence: 99%

B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway

et al. 2022

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“…It was also shown that B7-H3 promotes VEGFA expression and angiogenesis, which dependents on the NF-κB pathway in colorectal cancer (CRC), and CRC cell recruits regulatory T cells to promote chemoresistance via NF-κB signaling pathway (60). Besides, B7-H3 is also regulated by Th1, IL-4, IFN-gamma and TNF-alpha, which is an important cancer-promoting inflammatory molecule and significantly increases the release of soluble B7-H3 in colon cancer cell lines (61,62). Meanwhile, the B7-H3 pathway has a dual role in contributing to the regulation of innate immune responses.…”

Section: Discussionmentioning

confidence: 99%

A three-phase trans-ethnic study reveals B7-H3 expression is a significant and independent biomarker associated with colon cancer overall survival

Gao¹,

Xu²,

Gao³

et al. 2021

J Gastrointest Oncol

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Background: There have been inconsistent results and conflicting conclusions among the existing prognostic studies of B7-H3 expression in colon cancer patients. Therefore, the association between B7-H3 expression and colon cancer survival has remained largely unclear.Methods: We performed a three-phase and trans-ethnic prognostic study of B7-H3 expression in colon cancer patients involving perhaps the largest population to date. In the discovery phase, we utilized a Cox proportional hazards model adjusted for covariates to test the association between B7-H3 expression and colon cancer overall survival (OS) time in a European population from The Cancer Genome Atlas (TCGA) cohort (n=433). In the validation phase I, the association was replicated in a European population from Gene Expression Omnibus (GEO) cohort (n=811). In the validation phase II, we again confirmed the significant association in an Asian population from Fujian Medical University Union Hospital (UNION) cohort (n=179).Furthermore, a series of Kaplan-Meier analysis, bioinformatics analysis of tumor immune microenvironment (TIME), and immune checkpoint prognostic prediction analysis, as well as sensitivity analysis, were also conducted.Results: Highly expressed B7-H3 was a significant and robust biomarker to colon cancer survival, with a large hazard ratio (HR) [HR TCGA =4.60, 95% confidence interval (CI): 2.15 to 9.83, P=8.37×10 −05 ; HR GEO =1.47, 95% CI: 1.12 to 1.94, P=0.0056; HR UNION =1.63, 95% CI: 1.36 to 1.95, P=7.91×10 −08 ]. We detected an involvement of B7-H3 in the tumor immune microenvironment (TIME). Meanwhile, B7-H3 was significantly and weakly correlated with 6 out of 27 well-recognized immune checkpoint genes. Even after adjusting for effects of other immune checkpoint genes, B7-H3 still exhibited a harmful effect on colon cancer survival using samples from TCGA and GEO cohorts (HR =1.47, 95% CI: 1.07 to 2.02, P=0.0184), indicating that it was an independent prognostic factor of colon cancer. We also proposed an immune checkpoint prognostic risk score which possessed the capability to identify colon cancers with high risk of mortality. Conclusions:The expression of B7-H3 is a significant, robust, and independent prognostic factor to colon cancer OS.

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“…In the liver metastasis model of colorectal cancer, SIRT-1 attenuates the immunosuppressive ability of MSC and enhances its pro-inflammatory ability by inhibiting the expression of inducible nitric oxide synthase (iNOS) in mesenchymal stem cells by deacetylating p65, thereby increasing the number of CD8 + T cells to enhance local immunity and inhibit tumor development [ 66 ]. Inhibition of SIRT-1 upregulates B7-H3 and TNF-α in the tumor microenvironment, thereby inducing tumor immune escape [ 67 ]. SIRT-1 can inhibit Th17 differentiation by deacetylating STAT3, thereby slowing tumor growth.…”

Section: The Mechanism Of Nad Pathway Related Molecules In Timementioning

confidence: 99%

Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment

Liu

Mohseni

et al. 2022

Cancer Cell Int

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Nicotinamide adenine dinucleotide (NAD) is the core of cellular energy metabolism. NAMPT, Sirtuins, PARP, CD38, and other molecules in this classic metabolic pathway affect many key cellular functions and are closely related to the occurrence and development of many diseases. In recent years, several studies have found that these molecules can regulate cell energy metabolism, promote the release of related cytokines, induce the expression of neoantigens, change the tumor immune microenvironment (TIME), and then play an anticancer role. Drugs targeting these molecules are under development or approved for clinical use. Although there are some side effects and drug resistance, the discovery of novel drugs, the development of combination therapies, and the application of new technologies provide solutions to these challenges and improve efficacy. This review presents the mechanisms of action of NAD pathway-related molecules in tumor immunity, advances in drug research, combination therapies, and some new technology-related therapies.

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miR-34a induces immunosuppression in colorectal carcinoma through modulating a SIRT1/NF-κB/B7-H3/TNF-α axis

Cited by 26 publications

References 48 publications

B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway

B7‑H3 promotes the epithelial‑mesenchymal transition of NSCLC by targeting SIRT1 through the PI3K/AKT pathway

A three-phase trans-ethnic study reveals B7-H3 expression is a significant and independent biomarker associated with colon cancer overall survival

Mechanism research and treatment progress of NAD pathway related molecules in tumor immune microenvironment

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