The tumor-suppressive role of BATF2 in esophageal squamous cell carcinoma

Han, Tianci; Wang, Zhiyong; Yang, Yang; Shu, Tianci; Li, Weinan; Liu, Dali; Li, Peiwen; Qi, Ruiqun; Ren, Yi; Li, Li; Lv, Hong; Zhang, Shuguang; Zhang, Lin

doi:10.3892/or.2015.4090

Cited by 9 publications

(4 citation statements)

References 22 publications

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“…Interestingly, Batf2 in cancer cells has also been reported to be involved in cancer cell growth inhibition. For example, lower BATF2 expression is associated with a poor prognosis in hepatocellular carcinoma (26), oral tongue squamous cell carcinoma (27), esophageal squamous cell carcinoma (28), and medulloblastoma (29). BATF2 is down-regulated in various types of cancers and induces apoptosis (8).…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages

Kanemaru

Yamane

Fukushima

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The development of effective treatments against cancers is urgently needed, and the accumulation of CD8 T cells within tumors is especially important for cancer prognosis. Although their mechanisms are still largely unknown, growing evidence has indicated that innate immune cells have important effects on cancer progression through the production of various cytokines. Here, we found that () has an antitumor effect. An s.c. inoculated tumor model produced fewer IL-12 p40 macrophages and activated CD8 T cells within the tumors of mice compared with WT mice. In vitro studies also revealed that the IL-12 p40 expression was significantly lower in macrophages following their stimulation by toll-like receptor ligands, such as R848. Additionally, we found that BATF2 interacts with p50/p65 and promotes IL-12 p40 expression. In conclusion, has an antitumor effect through the up-regulation of IL-12 p40 in tumor-associated macrophages, which eventually induces CD8 T-cell activation and accumulation within the tumor.

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Section: Discussionmentioning

confidence: 99%

Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages

Kanemaru

Yamane

Fukushima

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The protein coded by BATF2 was shown to have an antitumor effect in a mouse model through upregulation of IL-12 p40 in tumor-associated macrophages, leading to CD8 + T-cell activation and tumor accumulation [ 27 ]. Among other cancers, BATF2 was demonstrated as a tumor suppressor of gastric cancer [ 28 ], glioblastoma [ 29 ], and esophageal squamous cell carcinoma [ 30 ]. In contrast, LY6E , the other gene found as upregulated in ASD blood samples, was suggested as a biomarker of poor prognosis in smoking-induced lung carcinogenesis [ 31 ] and colorectal cancer [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Blood RNA Sequencing Indicates Upregulated BATF2 and LY6E and Downregulated ISG15 and MT2A Expression in Children with Autism Spectrum Disorder

Voinsky

Zoabi

Shomron

et al. 2022

IJMS

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Mutations in over 100 genes are implicated in autism spectrum disorder (ASD). DNA SNPs, CNVs, and epigenomic modifications also contribute to ASD. Transcriptomics analysis of blood samples may offer clues for pathways dysregulated in ASD. To expand and validate published findings of RNA-sequencing (RNA-seq) studies, we performed RNA-seq of whole blood samples from an Israeli discovery cohort of eight children with ASD compared with nine age- and sex-matched neurotypical children. This revealed 10 genes with differential expression. Using quantitative real-time PCR, we compared RNAs from whole blood samples of 73 Israeli and American children with ASD and 26 matched neurotypical children for the 10 dysregulated genes detected by RNA-seq. This revealed higher expression levels of the pro-inflammatory transcripts BATF2 and LY6E and lower expression levels of the anti-inflammatory transcripts ISG15 and MT2A in the ASD compared to neurotypical children. BATF2 was recently reported as upregulated in blood samples of Japanese adults with ASD. Our findings support an involvement of these genes in ASD phenotypes, independent of age and ethnicity. Upregulation of BATF2 and downregulation of ISG15 and MT2A were reported to reduce cancer risk. Implications of the dysregulated genes for pro-inflammatory phenotypes, immunity, and cancer risk in ASD are discussed.

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“…Abnormalities in BATF-2 and cellular communication network factor 1 (CCN1) expressions and their correlation are closely associated with malignant behaviors of colorectal cancer cells, affecting the prognosis of patients [ 9 , 10 ]. Moreover, in other tumors such as hepatocellular carcinoma (HCC) [ 11 ], non-small-cell lung cancer (NSCLC) [ 12 ], esophageal squamous cell carcinoma (ESCC) [ 13 ] and gastric cancer (GC) [ 14 ], the down-regulation of BATF-2 expression is associated with a poor prognosis. Wang et al found that BATF-2 regulated the epithelial-mesenchymal transition (EMT) and lung adenocarcinoma (LUAD) metastasis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer

et al. 2021

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Background Basic leucine zipper ATF-like transcription factor 2 (BATF2) has been reported to participate in the occurrence and development of some malignancies. Herein, we aimed to explore the expression pattern and clinical implications of BATF2 in breast cancer (BC). Methods We assessed the differences in BATF2 mRNA expression between cancerous and noncancerous tissues in BC using GEPIA and UALCAN data and in BATF2 protein expression pattern using Human Protein Atlas (HPA) data. BATF2 co-expression networks were analyzed in Coexpedia. The association between the differentially expressed BATF2 mRNA and BC prognosis was assessed using UALCAN, OSbrca, and GEPIA databases. In external validations, BATF2 protein expression in BC tissues was quantitated using a tissue microarray and immunohistochemistry (IHC) analysis, and BATF2 mRNA expression in serum and serum-derived exosomes of BC patients using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results No difference in the BATF2 mRNA expression level was found between cancerous and noncancerous tissues in BC based on databases. There were low-to-moderate levels of increases in BATF2 protein expressions in BC cases from the HPA cohort. BATF2 mRNA expression was negatively correlated with androgen receptor (AR) and positively correlated with BRCA2 DNA repair associated (BRCA2), marker of proliferation Ki-67 (Mki67), and tumor protein p53 (TP53) expressions. Generally, BATF2 mRNA exhibited a non-significant association with BC prognosis; yet the subgroup analyses showed that triple-negative breast cancer (TNBC) patients with high BATF2 mRNA expressions had a longer overall survival (OS). Our IHC analysis revealed a positive rate of BATF2 protein expression of 46.90%, mainly located in the nucleus of cancer cells in BC, and the OS of BC patients with high BATF2 protein expressions was prolonged. The positive rates of BATF2 mRNA expressions in the serum and exosomes were 45.00 and 41.67%, respectively. Besides, the AUCs of serum and exosomal BATF2 mRNA for BC diagnosis were 0.8929 and 0.8869, respectively. Conclusions BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.

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The tumor-suppressive role of BATF2 in esophageal squamous cell carcinoma

Cited by 9 publications

References 22 publications

Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages

Antitumor effect of Batf2 through IL-12 p40 up-regulation in tumor-associated macrophages

Blood RNA Sequencing Indicates Upregulated BATF2 and LY6E and Downregulated ISG15 and MT2A Expression in Children with Autism Spectrum Disorder

Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer

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