B7-H3 is spliced by SRSF3 in colorectal cancer

Zhang, Chunxia; Chen, Yinshuang; Li, Fuchao; Yang, Man; Fang, Meng; Zhang, Yawen; Chen, Weichang; Wang, Weipeng

doi:10.1007/s00262-020-02683-9

Cited by 19 publications

(9 citation statements)

References 48 publications

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“…Experimental studies in mice showed that induction of colitis and water avoidance stress affect levels of Mir29a and Mir29b and intestinal permeability in wildtype mice (71). Despite inconsistent results and conflicting conclusions of existing prognostic studies of B7-H3 (22,(24)(25)(26)(27)(28)(29)(30)(32)(33)(34)(35)(36)(37), our study, with the largest sample size, confirmed that it was a significant and independent biomarker to colon cancer survival by several trans-ethnical validations.…”

Section: Discussionsupporting

confidence: 63%

“…An array of studies have indicated that highly expressed B7-H3 promotes tumor progression and metastasis, as well as being associated with poor prognosis in various of cancers, including glioma (15), hepatocellular carcinoma (16), lung cancer (17), breast cancer (18), osteosarcoma (19), cutaneous melanoma (20), and pancreatic cancer (21). However, the results of existing prognostic studies of B7-H3 expression and colon cancer (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) have been inconsistent and have presented conflicting conclusions; thus, we believe there is an urgent need to elaborate the effect of B7-H3 on colon cancer survival. Besides, various technical bottlenecks of previous studies need to be addressed: (I) there have been very few European studies (22,23,29), and majority of these studies were conducted among Asian populations (24)(25)(26)(27)(28)(30)(31)(32)(33)(34)(35)(36)(37); (II) no study so far has focused on the non-linear effects of B7-H3 on colon cancer survival, with previous studies simply having tested its linear effect; (III) there has been no independent validation of B7-H3, the association has consistently been evaluated in a single population; and (IV) there have been no trans-ethnic population studies of B7-H3 thus far.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

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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“…B7-H3 is one of the negative costimulatory molecules in the B7 family, and its abnormal expression disrupts the balance of T cell immune response, thus mediating tumor immune escape. Numerous studies have shown that B7-H3 protein is abnormally high expressed in colorectal cancer [15] , prostate cancer [16] , pancreatic cancer [17] , squamous cell carcinoma [18] , non-small cell lung cancer [19] , gastric cancer [20,21] and other tumors, and its expression has significant clinical significance.…”

Section: Discussionmentioning

confidence: 99%

“…A study shows that the expression level of B7-H3 in colorectal cancer is negatively correlated with tumor size and prognosis [15] . Moreover, the positive expression rate of B7-H3 in ovarian cancer is more than 90% and is significantly associated with tumor stage, high recurrence rate, and low survival rate [22] .…”

Section: Discussionmentioning

confidence: 99%

A4GALT mediated the glycosylation of B7-H3 in human colorectal cancer cell lines

Han

Chen³

et al. 2022

Preprint

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B7-H3 is one of the most important members of the B7/CD28 family, and its expression level is abnormally high in a variety of tumors. B7-H3 inhibits T cell activation via binding to the corresponding receptors on T cells, thereby mediating tumor immune escape. Glycosylation is a common post-translational modification of proteins, which plays an essential role in protein expression patterns and biological functions. Current evidence has shown that the abnormal glycosylation of B7-H3 in tumors is of great significance for protein expression and ligand-receptor binding. Therefore, in-depth exploration of the underlying mechanism of glycosylation modification of B7-H3 is expected to provide new insights for tumor immunotherapy. To investigate the underlying mechanism of glycosyltransferase-mediated glycosylation of B7-H3. Firstly, the CHIPBase database was used to screen glycosyltransferases with a high correlation with the protein expression of B7-H3. Then their siRNAs were designed and synthesized to transfect into cells, and the western blotting assay was performed for further screening. Secondly, the siRNA and overexpression plasmid of the screened glycosyltransferase were respectively transfected into cells to verify the effect on the expression level of B7-H3. Thirdly, the effect of glycosyltransferase on the expression level of B7-H3 was explored by changing its substrate level. Finally, the co-immunoprecipitation experiment was conducted to verify whether protein binding existed between B7-H3 and the glycosyltransferase. The glycosyltransferase called A4GALT had the highest correlation with the protein expression of B7-H3. After knocking down or overexpressing A4GALT, the protein expression level of B7-H3 both changed significantly. When knocked down GALT to reduce the galactosyl donors, B7-H3 was significantly down-regulated. And B7-H3 was up-regulated while increasing the galactose in the medium. In addition, the Co-immunoprecipitation experiment proved that there was protein binding between B7-H3 and A4GALT. A4GALT can positively regulate the expression of B7-H3, and changing the level of galactosyl donors can also positively regulate the expression of B7-H3. There is a protein interaction between A4GALT and B7-H3.

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“…This T-UCR was selected because of its sequence and expression conservation in the nervous systems of the abovementioned species, and its UCR sequence is located in the intronic region of the protein-coding gene Srsf3. Srsf3 is an extremely important RNA splicing factor that helps to regulate the expression of many important genes and plays a role in the occurrence and development of a variety of cancers ( Kumar et al, 2019 ; Fuentes-Fayos et al, 2020 ; Zhang et al, 2021 ). The latest study identified Srsf3 as a potential cancer treatment target ( Zhou et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Long Non-coding RNA T-uc.189 Modulates Neural Progenitor Cell Fate by Regulating Srsf3 During Mouse Cerebral Cortex Development

Zhang

Zhou

et al. 2021

Front. Neurosci.

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Neurogenesis is a complex process that depends on the delicate regulation of spatial and temporal gene expression. In our previous study, we found that transcribed ultra-conserved regions (T-UCRs), a class of long non-coding RNAs that contain UCRs, are expressed in the developing nervous systems of mice, rhesus monkeys, and humans. In this study, we first detected the full-length sequence of T-uc.189, revealing that it was mainly concentrated in the ventricular zone (VZ) and that its expression decreased as the brain matured. Moreover, we demonstrated that knockdown of T-uc.189 inhibited neurogenesis. In addition, we found that T-uc.189 positively regulated the expression of serine-arginine-rich splicing factor 3 (Srsf3). Taken together, our results are the first to demonstrate that T-uc.189 regulates the expression of Srsf3 to maintain normal neurogenesis during cortical development.

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B7-H3 is spliced by SRSF3 in colorectal cancer

Cited by 19 publications

References 48 publications

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

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

A4GALT mediated the glycosylation of B7-H3 in human colorectal cancer cell lines

Long Non-coding RNA T-uc.189 Modulates Neural Progenitor Cell Fate by Regulating Srsf3 During Mouse Cerebral Cortex Development

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