Aberrant super-enhancer-driven oncogene ENC1 promotes the radio-resistance of breast carcinoma
| Autor: | Guangcheng Guo, Nan Wang, Lin Li, Mingzhi Zhu, Fang Wang, Youyi Xiong, Xinxing Wang, Yuanyan Gu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Transcriptional Activation
Cancer Research Immunology Mice Nude Breast Neoplasms Protein Serine-Threonine Kinases Radiation Tolerance Article Histones Cellular and Molecular Neuroscience Breast cancer Transcription Factor 4 GLI1 Cell Line Tumor Animals Humans Luciferase Neoplasm Metastasis RNA Small Interfering YAP1 Hippo signaling pathway Mice Inbred BALB C biology Oncogene QH573-671 Lysine Microfilament Proteins Neuropeptides Intracellular Signaling Peptides and Proteins Nuclear Proteins Acetylation YAP-Signaling Proteins Cell Biology TCF4 Epigenome Oncogenes Prognosis CTGF Gene Expression Regulation Neoplastic Enhancer Elements Genetic Transcriptional Coactivator with PDZ-Binding Motif Proteins Cancer research biology.protein Female Cytology |
| Zdroj: | Cell Death and Disease, Vol 12, Iss 8, Pp 1-13 (2021) Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Poor response of tumors to radiotherapy is a major clinical obstacle. Because of the dynamic characteristics of the epigenome, identification of possible epigenetic modifiers may be beneficial to confer radio-sensitivity. This research was set to examine the modulation of ectodermal-neural cortex 1 (ENC1) in radio-resistance in breast carcinoma (BC). In silico identification and immunohistochemical staining revealed that overexpression of ENC1 promoted BC metastasis to the bone and brain. Moreover, its overexpression promoted the translocation of YAP1/TAZ into the nucleus and enhanced expression of GLI1, CTGF, and FGF1 through the Hippo pathway. ENC1 expression was controlled by a ~10-kb long SE. ENC1-SEdistal deletion reduced ENC1 expression and inhibited the malignant behavior of BC cells and their resistance to radiotherapy. The binding sites on the ENC1-SE region enriched the shared sequence between TCF4 and ENC1 promoter. Knocking-down TCF4 inhibited luciferase activity and H3K27ac-enriched binding of the ENC1-SE region. Additionally, SE-driven ENC1 overexpression mediated by TCF4 may have clinical implications in radio-resistance in BC patients. Our findings indicated that ENC1 overexpression is mediated by SE and the downstream TCF4 to potentiate the Hippo/YAP1/TAZ pathway. Targeting this axis might be a therapeutic strategy for overcoming BC radio-resistance. |
| Databáze: | OpenAIRE |
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