Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1
Background. Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identi...
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2023/3804605 |
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| author | Kunlong Zhang Jun Lu Fang Fang Yongping Zhang Juanjuan Yu Yanfang Tao Wenyuan liu Lihui Lu Zimu Zhang Xinran Chu Jianwei Wang Xiaolu Li Yuanyuan Tian Zhiheng Li Qian Li Xu Sang Li Ma Ningling Wang Jian Pan Shaoyan Hu |
| author_facet | Kunlong Zhang Jun Lu Fang Fang Yongping Zhang Juanjuan Yu Yanfang Tao Wenyuan liu Lihui Lu Zimu Zhang Xinran Chu Jianwei Wang Xiaolu Li Yuanyuan Tian Zhiheng Li Qian Li Xu Sang Li Ma Ningling Wang Jian Pan Shaoyan Hu |
| author_sort | Kunlong Zhang |
| collection | DOAJ |
| description | Background. Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identity and the pathogenesis of multiple cancers. Belonging to the cytosolute linker protein group, FYB1 is essential for TCR signaling and extensively studied in terms of tumor pathogenesis and metastasis. Dissecting the role of FYN binding protein 1 (FYB1) in T-ALL holds the potential to improve the treatment outcome and prognosis of T-ALL. Methods. In this study, SEs were explored using public H3K27ac ChIP-seq data derived from T-ALL cell lines, AML cell lines and hematopoietic stem and progenitor cells (HSPCs). Downstream target of FYB1 gene was identified by RNA-seq. Effects of shRNA-mediated downregulation of FYB1 and immunoglobulin lambda-like polypeptide 1 (IGLL1) on self-renewal of T-ALL cells were evaluated in vitro and/or in vivo. Results. As an SE-driven gene, overexpression of FYB1 was observed in T-ALL, according to the Cancer Cell Line Encyclopedia database. In vitro, knocking down FYB1 led to comprised growth and enhanced apoptosis of T-ALL cells. In vivo, downregulation of FYB1 significantly decreased the disease burden by suppressing tumor growth and improved survival rate. Knocking down FYB1 resulted in significantly decreased expression of IGLL1 that was also an SE-driven gene in T-ALL. As a downstream target of FYB1, IGLL1 exerted similar role as FYB1 in inhibiting growth of T-ALL cells. Conclusion. Our results suggested that FYB1 gene played important role in regulating self-renewal of T-ALL cells by activating IGLL1, representing a promising therapeutic target for T-ALL patients. |
| format | Article |
| id | doaj-art-718043b86f6d483cbca6c4e4fc999fc5 |
| institution | Kabale University |
| issn | 2314-7156 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-718043b86f6d483cbca6c4e4fc999fc52025-08-20T03:33:57ZengWileyJournal of Immunology Research2314-71562023-01-01202310.1155/2023/3804605Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1Kunlong Zhang0Jun Lu1Fang Fang2Yongping Zhang3Juanjuan Yu4Yanfang Tao5Wenyuan liu6Lihui Lu7Zimu Zhang8Xinran Chu9Jianwei Wang10Xiaolu Li11Yuanyuan Tian12Zhiheng Li13Qian Li14Xu Sang15Li Ma16Ningling Wang17Jian Pan18Shaoyan Hu19Children’s Hospital of Soochow UniversityDepartment of HematologyInstitute of Pediatric ResearchChildren’s Hospital of Soochow UniversityChildren’s Hospital of Soochow UniversityInstitute of Pediatric ResearchDepartment of PediatricsChildren’s Hospital of Soochow UniversityInstitute of Pediatric ResearchDepartment of HematologyInstitute of Pediatric ResearchInstitute of Pediatric ResearchDepartment of HematologyChildren’s Hospital of Soochow UniversityChildren’s Hospital of Soochow UniversityChildren’s Hospital of Soochow UniversityChildren’s Hospital of Soochow UniversityDepartment of PediatricsInstitute of Pediatric ResearchDepartment of HematologyBackground. Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identity and the pathogenesis of multiple cancers. Belonging to the cytosolute linker protein group, FYB1 is essential for TCR signaling and extensively studied in terms of tumor pathogenesis and metastasis. Dissecting the role of FYN binding protein 1 (FYB1) in T-ALL holds the potential to improve the treatment outcome and prognosis of T-ALL. Methods. In this study, SEs were explored using public H3K27ac ChIP-seq data derived from T-ALL cell lines, AML cell lines and hematopoietic stem and progenitor cells (HSPCs). Downstream target of FYB1 gene was identified by RNA-seq. Effects of shRNA-mediated downregulation of FYB1 and immunoglobulin lambda-like polypeptide 1 (IGLL1) on self-renewal of T-ALL cells were evaluated in vitro and/or in vivo. Results. As an SE-driven gene, overexpression of FYB1 was observed in T-ALL, according to the Cancer Cell Line Encyclopedia database. In vitro, knocking down FYB1 led to comprised growth and enhanced apoptosis of T-ALL cells. In vivo, downregulation of FYB1 significantly decreased the disease burden by suppressing tumor growth and improved survival rate. Knocking down FYB1 resulted in significantly decreased expression of IGLL1 that was also an SE-driven gene in T-ALL. As a downstream target of FYB1, IGLL1 exerted similar role as FYB1 in inhibiting growth of T-ALL cells. Conclusion. Our results suggested that FYB1 gene played important role in regulating self-renewal of T-ALL cells by activating IGLL1, representing a promising therapeutic target for T-ALL patients.http://dx.doi.org/10.1155/2023/3804605 |
| spellingShingle | Kunlong Zhang Jun Lu Fang Fang Yongping Zhang Juanjuan Yu Yanfang Tao Wenyuan liu Lihui Lu Zimu Zhang Xinran Chu Jianwei Wang Xiaolu Li Yuanyuan Tian Zhiheng Li Qian Li Xu Sang Li Ma Ningling Wang Jian Pan Shaoyan Hu Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1 Journal of Immunology Research |
| title | Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1 |
| title_full | Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1 |
| title_fullStr | Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1 |
| title_full_unstemmed | Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1 |
| title_short | Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1 |
| title_sort | super enhancer regulatory gene fyb1 promotes the progression of t cell acute lymphoblastic leukemia by activating igll1 |
| url | http://dx.doi.org/10.1155/2023/3804605 |
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