| Project/Area Number |
21K16142
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Kanazawa University (2023)
Kyoto University (2021) |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | C/EBP-alpha / CXCL13 / Super-enhancer / p53 / CXCR5 / Chromosome conformation / Tumor protein / DNA damage / Epigenetics / Transcription / Homeostasis / lung homeostasis / chromosomes conformation / CCAAT enhancer / Cohesin |
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| Outline of Research at the Start |
During lung injury, the emergent gene expression in AT2 cells is required for lung homeostasis. What mechanisms regulate the emergent gene expression lung homeostasis is elusive. C/EBPa is specific transcriptional factor known to regulate the emergent gene expression in AT2 cell.
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| Outline of Final Research Achievements |
As per the cancer genome atlas, the C/EBP-alpha in amplified and over expressed in many cancers. Hydroxyurea (HU) treatment of lung adenocarcinoma A549 cells exhibited C/EBP-alpha's role in promoting the cell viability, suggesting the role of C/EBP-alpha in chemotherapeutic resistance. Ongoing RNA-sequencing of HU-treated 293T cells aims to identify C/EBP-alpha induced genes vital for cell survival. This will allow identifying novel therapeutic targets for treatment of C/EBP-alpha overexpressing cancers. A parallel investigation also uncovered a super enhancer region driving aberrant CXCL13 expression in human cancers. The autocrine signaling in CXCR5-CXCL13 amplified cancers can lead to chemotherapeutic resistance. Several p53 target genes were down regulated by CXCR5-CXCL13 axis in human cancer cells of B-lymphoma origin, Colorectal cancer origin and liver cancer origin. This research identified CXCR5-CXCL13 axis as a new target to overcome the chemotherapeutic resistance in cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
This study explores the role of C/EBP-alpha in cell survival, chemotherapeutic resistance under the DNA-replication stress. The study also explores the mechanism underlying aberrant CXCL13 expression in human cancers. Both findings offer insights into therapeutic avenues for combating human cancers.
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