TCF12 activates MAGT1 expression to regulate the malignant progression of pancreatic carcinoma cells

Tang, Yanjiao; Wu, Hongyi; Shan, Guiqiu

doi:10.3892/ol.2021.13180

Cited by 6 publications

(4 citation statements)

References 32 publications

(55 reference statements)

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“…However, two of our pNETs did not express either PDX1 or ARX . Pnet4 displayed differential activity of TCF12 , which has been implicated in pancreatic and gastrointestinal cancer proliferation and invasion, while pnet3’s top regulon, RARB , was previously found to direct differentiation of embryonic stem cells to pancreatic endocrine cells in vitro ( 20 , 21 ). Few common TFs were identified across NET samples, revealing the heterogeneity within and between GEP-NETs from different anatomical sites.…”

Section: Resultsmentioning

confidence: 99%

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors

Hoffman,

Dowrey,

Villacorta Martin

et al. 2023

Sci. Adv.

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Neuroendocrine tumors (NETs) are rare cancers that most often arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP)–NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation, and fate determination stages. Tumor and lymphoid compartments sparsely expressed immunosuppressive targets commonly investigated in clinical trials, such as the programmed cell death protein–1/programmed death ligand–1 axis. However, infiltrating myeloid cell types within both primary and metastatic GEP-NETs were enriched for genes encoding other immune checkpoints, including VSIR (VISTA), HAVCR2 (TIM3), LGALS9 (Gal-9), and SIGLEC10 . Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

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Section: Resultsmentioning

confidence: 99%

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors

Hoffman,

Dowrey,

Villacorta Martin

et al. 2023

Sci. Adv.

View full text Add to dashboard Cite

show abstract

“…However, two of our pNETs did not express either PDX1 or ARX . Pnet4 displayed differential activity of TCF12 , which has been implicated in pancreatic and gastrointestinal cancer proliferation and invasion, while pnet3’s top regulon, RARB , was previously found to direct differentiation of embryonic stem cells to pancreatic endocrine cells in vitro ( 20, 21 ). Few common transcription factors were identified across NET samples, revealing the heterogeneity within and between GEP-NETs from different anatomical sites.…”

Section: Resultsmentioning

confidence: 99%

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors

Hoffman

Dowrey

Martin

et al. 2022

Preprint

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Neuroendocrine tumors (NETs) are rare cancers that may arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic (GEP) NET growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we investigated the single-cell transcriptomes of tumor and immune cells from patients with gastroenteropancreatic NETs. Malignant GEP-NET cells expressed genes and regulons associated with normal, gastrointestinal endocrine cell differentiation and fate determination stages. While tumor and lymphoid compartments sparsely expressed immunosuppressive targets, infiltrating myeloid cells were enriched for alternative immunotherapy pathways including VSIR, Tim3/Gal9, and SIGLEC10. Finally, analysis of paired primary and metastatic tissue specimens from small intestinal NETs demonstrated transcriptional transformation between the primary tumor and its distant metastasis. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

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“…TCF12 is a transcription factor (TF) that can bind to various gene promoters and regulate processes such as embryonic development. Moreover, TCF12 has been proved as an oncogene in different tumors, including pancreatic carcinoma, 34 melanoma, 35 and hepatocellular carcinoma. 36 Consistent with previous findings, 37 we found that TCF12 silence could inhibit the malignant phenotype of gliomas.…”

Section: (G H)mentioning

confidence: 99%

RNA‐binding protein DHX9 promotes glioma growth and tumor‐associated macrophages infiltration via TCF12

et al. 2022

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Background: Glioma is the most common malignant tumor of the central nervous system, with high heterogeneity, strong invasiveness, high therapeutic resistance, and poor prognosis, comprehending a serious challenge in neuro-oncology. Until now, the mechanisms underlying glioma progression have not been fully elucidated. Methods:The expression of DExH-box helicase 9 (DHX9) in tissues and cells was detected by qRT-PCR and western blot. EdU and transwell assays were conducted to assess the effect of DHX9 on proliferation, migration and invasion of glioma cells.Cocultured model was used to evaluate the role of DHX9 on macrophages recruitment and polarization. Animal study was performed to explore the role of DHX9 on macrophages recruitment and polarization in vivo. Bioinformatics analysis, dualluciferase reporter assay and chromatin immunoprecipitation (ChIP)-qPCR assay was used to explore the relation between DHX9 and TCF12/CSF1.Results: DHX9 was elevated in gliomas, especially in glioblastoma multiforme (GBM).Besides promoting the proliferation, migration, and invasion of glioma cells, DHX9 facilitated the infiltration of macrophages into glioma tissues and polarization to M2-like macrophages, known as tumor-associated macrophages (TAMs). DHX9 silencing decreased the expression of colony-stimulating factor 1 (CSF1), which partially restored the inhibitory effect on malignant progress of glioma and infiltration of TAMs caused by DHX9 knockdown by targeting the transcription factor 12 (TCF12). Moreover, TCF12 could directly bind to the promoter region of CSF1. Conclusion: DHX9/TCF12/CSF1 axis regulated the increases in the infiltration ofTAMs to promote glioma progression and might be a novel potential target for future immune therapies against gliomas.

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TCF12 activates MAGT1 expression to regulate the malignant progression of pancreatic carcinoma cells

Cited by 6 publications

References 32 publications

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors

Intertumoral lineage diversity and immunosuppressive transcriptional programs in well-differentiated gastroenteropancreatic neuroendocrine tumors

RNA‐binding protein DHX9 promotes glioma growth and tumor‐associated macrophages infiltration via TCF12

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