Cancer germline antigen gene MAGEB2 promotes cell invasion and correlates with immune microenvironment and immunotherapeutic efficiency in laryngeal cancer

et al. 2022

Cell Death Dis

Zinc finger proteins (ZNFs) have been demonstrated to participate extensively in breast cancer progression by functioning as transcription factors, but there are still a variety of ZNFs whose biological mechanisms remain unknown. Here, we show that zinc finger protein 276 (ZNF276) is highly expressed in breast cancer tissues and cell lines. Higher level of ZNF276 correlated with poor prognosis. Gain-of and loss-of function suggested that ZNF276 is essential for the proliferation, migration and invasion of breast cancer cells in vitro and metastasis in vivo. RNA-sequencing and CUT&Tag assay revealed that ZNF276 controlled a variety of growth and metastasis-related genes expression. ZNF276 transcriptionally promoted the expression of CYP1B1 by directly binds to the promoter region of the CYP1B1 through its C2H2 domain. ZNF276 facilitated the translocation of β-catenin from cytoplasm to nucleus through CYP1B1, leading to the upregulation of cyclin D1 and c-Myc, and the activation of the Wnt/β-catenin pathway. Knockdown of CYP1B1 significantly blocked the ZNF276-mediated effects on cell proliferation, migration and invasion. Lastly, ZNF276 interacted with MAGEB2 which enhanced the binding of ZNF276 at the CYP1B1 promoter, promoted CYP1B1 expression and Wnt signaling activation. Collectively, these findings highlight the oncogenic role of ZNF276 on breast cancer cell proliferation and metastasis. Targeting ZNF276/MAGEB2 axis may serve as a potential therapeutic strategy for breast cancer patients.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ZNF276 promotes the malignant phenotype of breast carcinoma by activating the CYP1B1-mediated Wnt/β-catenin pathway

Lei

et al. 2022

Cell Death Dis

“…We hypothesise that MAGEB2 could act at the level of two mechanisms of action largely mediated by the GAGE family: (i) ability to create a more “open” chromatin structure by up-regulating histone 3 lysine 56 (H3K56Ac) acetylation, which could increase the efficiency of DNA repair, as described in a model of radioresistance in ovarian cancer or (ii) MAGEB2 could promote the development of immunosuppressive EMT (e.g., by down-regulating the expression of CXCL9 and CXCL10) and decreasing the recruitment of effector CD8+ T cells, thereby exerting resistance to checkpoint immunotherapy. Alternatively, MAGEB2 could induce stemness characteristics by modulating the HDAC1 levels [ 56 , 57 , 58 ]. The observed oncogenic effect of MAGEB2 promoting resistance correlates with other described aspects of MAGEB2 promoting the cell proliferation in tumour cells.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, MAGEB2 plays a role in enhancing the ribosome biogenesis as part of its repertoire to support cancer cell proliferation and is epigenetically activated in HNSCC [ 21 , 60 ]. Interestingly, the MAGEB2 expression has been associated with the inflammatory response in tumour laryngeal tissue [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic and Proteomic Profiles for Elucidating Cisplatin Resistance in Head-and-Neck Squamous Cell Carcinoma

García-Mayea

Benítez-Álvarez

Sánchez-García

et al. 2022

Cancers

To identify the novel genes involved in chemoresistance in head and neck squamous cell carcinoma (HNSCC), we explored the expression profiles of the following cisplatin (CDDP) resistant (R) versus parental (sensitive) cell lines by RNA-sequencing (RNA-seq): JHU029, HTB-43 and CCL-138. Using the parental condition as a control, 30 upregulated and 85 downregulated genes were identified for JHU029-R cells; 263 upregulated and 392 downregulated genes for HTB-43-R cells, and 154 upregulated and 68 downregulated genes for CCL-138-R cells. Moreover, we crossed-checked the RNA-seq results with the proteomic profiles of HTB-43-R (versus HTB-43) and CCL-138-R (versus CCL-138) cell lines. For the HTB-43-R cells, 21 upregulated and 72 downregulated targets overlapped between the proteomic and transcriptomic data; whereas in CCL-138-R cells, four upregulated and three downregulated targets matched. Following an extensive literature search, six genes from the RNA-seq (CLDN1, MAGEB2, CD24, CEACAM6, IL1B and ISG15) and six genes from the RNA-seq and proteomics crossover (AKR1C3, TNFAIP2, RAB7A, LGALS3BP, PSCA and SSRP1) were selected to be studied by qRT-PCR in 11 HNSCC patients: six resistant and five sensitive to conventional therapy. Interestingly, the high MAGEB2 expression was associated with resistant tumours and is revealed as a novel target to sensitise resistant cells to therapy in HNSCC patients.

“…The neoantigen and TMB data (based on somatic mutation data) of HNC patients in the TCGA dataset were retrieved from The Cancer Immunome Atlas (TCIA) (https://tcia.at/home). 10 The MSI score was collected from published studies 14 . Then, we detect the above biomarkers differences between different GPRASP1 subgroups.…”

Section: Methodsmentioning

confidence: 99%

GPRASP1 is a candidate anti‐oncogene and correlates with immune microenvironment and immunotherapeutic efficiency in head and neck cancer

Liu

J Oral Pathology Medicine

et al. 2022

Self Cite

Background: G-protein-coupled receptor-associated sorting protein 1 (GPRASP1) plays an important role in tumorigenesis. However, GPRASP1 specific role has not been clarified in head and neck cancer (HNC).Methods: HNC RNA sequencing (RNA-seq) datasets, DNA methylation data, somatic mutation data, copy number variation (CNV) data, and corresponding clinicopathologic information were acquired from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A comprehensive evaluation was performed to explore the relationship of GPRASP1 expression with clinicopathologic characteristics, CNV, and DNA methylation. Additionally, we employed HNC tissue microarray (TMA) to further confirm the relation between GPRASP1 expression and clinical features. Then, we systematically associated the GPRASP1 with immunological properties from numerous perspectives, such as immune cell infiltration, immune-related pathways, immune checkpoint inhibitors (ICIs), immunomodulators, immunogenicity, and immunotherapy.Results: Analyzing TCGA, GEO, and TMA datasets, GPRASP1 is significantly downregulated in HNC compared to normal tissues. The expression of GPRASP1 is significantly negatively correlated with clinical features (perineural invasion, histologic grade, T stage, and TNM stage), and is an independent predictor of favorable prognosis, regardless of other clinicopathological features (HR: 0.42, 95% CI 0.20-0.91, p = 0.028). The etiological investigation found that the abnormal expression of GPRASP1 was related to DNA methylation, not CMV. Subsequently, the high expression of GPRASP1 was significantly correlated with immune cell infiltration (CD8 + T cell, tumor infiltrating lymphocyte), immune-related pathways (cytolytic activity, check-point, human leukocyte antigen), ICIs (CTLA4, HAVCR2, LAG3, PDCD1, and TIGIT), immunomodulators (CCR4/5, CXCL9, CXCR3/4/5), and immunogenicity (immune score, neoantigen, tumor mutation burden). Finally, immunophenoscore and