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Different roles of C/EBP-alpha in chromosome conformation during lung injury of young and old mice

Research Project

Project/Area Number 21K16142
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionKanazawa University (2023)
Kyoto University (2021)

Principal Investigator

Gothwal Santosh Kumar  金沢大学, 新学術創成研究機構, 特任助教 (80870526)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
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)
KeywordsC/EBP-alpha / CXCL13 / Super-enhancer / p53 / CXCR5 / Chromosome conformation / Tumor protein / DNA damage / Epigenetics / Transcription / Homeostasis / lung homeostasis / chromosomes conformation / CCAAT enhancer / Cohesin
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.

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.

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.

Report

(2 results)
  • 2023 Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (2 results)

All 2022

All Presentation (1 results) (of which Int'l Joint Research: 1 results) Funded Workshop (1 results)

  • [Presentation] A mutant p53 P72R driven modulation of CXCR5-CXCL13 axis in human B cell lymphoma-migration2022

    • Author(s)
      Santosh Kumar Gothwal
    • Organizer
      18th International p53 Workshop
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Funded Workshop] 18th International p53 workshop2022

    • Related Report
      2021 Research-status Report

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Published: 2021-04-28   Modified: 2025-01-30  

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