Characterization of the oncogenic potential of circRNAs in melanoma

黑色素瘤中 circRNA 致癌潜力的表征

基本信息

  • 批准号:
    10355644
  • 负责人:
  • 金额:
    $ 23.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-01-01 至 2023-12-31
  • 项目状态:
    已结题

项目摘要

SUMMARY Over the last decade noncoding RNAs (ncRNAs) have emerged as prominent players that are involved in the regulation of most, if not all, biological processes. Given their important roles, it is conceivable that ncRNAs contribute to the development of diseases such as cancer. Circular RNAs (circRNAs) are ncRNAs that are formed through alternative splicing of linear pre-mRNAs via a process termed backsplicing. circRNAs are abundant, stable, and evolutionarily conserved and display cell-type specific expression patterns, indicating that they may play important roles in cell homeostasis, differentiation, development, and disease. However, the formation of circRNAs, their regulation, and their functions are poorly understood, partially due to the lack of tools to drive permanent ectopic expression of circRNAs. We have developed genetic tools for stable overexpression of candidate circRNAs in vitro and in vivo, which we will implement as part of this R21 proposal. Using these tools, we will determine the oncogenic potential of two circRNAs we hypothesize to promote melanomagenesis. We identified circPMS1 and circDNAJC2 as candidate melanoma oncogenes by a comprehensive circRNA expression analysis in benign melanocytes and malignant melanoma cells. We will test if overexpression of these circDNAs promotes melanocyte transformation in vitro and tumor formation in our high-throughput melanoma mouse models. We will also begin the molecular characterization of the functions underlying circPMS1 and circDNAJC2 oncogenic activity, with an emphasis on peptide translation and miRNA sponging. Moreover, we will specifically silence circPMS1 and circDNAJC2 in human melanoma cells in vitro as well as in xenograft models to examine if circRNA expression is required for maintaining the transformed state and continued melanoma growth, respectively. Our proposed studies will demonstrate that overexpression of circPMS1 or circDNAJC2 drives melanomagenesis and establish an easily adaptable experimental framework that will pave the way for future studies of oncogenic circRNAs.
总结

项目成果

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Florian Karreth其他文献

Florian Karreth的其他文献

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{{ truncateString('Florian Karreth', 18)}}的其他基金

Characterization of the oncogenic potential of circRNAs in melanoma
黑色素瘤中 circRNA 致癌潜力的表征
  • 批准号:
    10542664
  • 财政年份:
    2022
  • 资助金额:
    $ 23.63万
  • 项目类别:
Chromosome 1q ceRNAs in Melanoma Progression and Metastasis
黑色素瘤进展和转移中的染色体 1q ceRNA
  • 批准号:
    10183657
  • 财政年份:
    2021
  • 资助金额:
    $ 23.63万
  • 项目类别:
Exploring miR-29 in melanoma progression and prevention
探索 miR-29 在黑色素瘤进展和预防中的作用
  • 批准号:
    10290462
  • 财政年份:
    2021
  • 资助金额:
    $ 23.63万
  • 项目类别:
Exploring miR-29 in melanoma progression and prevention
探索 miR-29 在黑色素瘤进展和预防中的作用
  • 批准号:
    10456977
  • 财政年份:
    2021
  • 资助金额:
    $ 23.63万
  • 项目类别:
Chromosome 1q ceRNAs in Melanoma Progression and Metastasis
黑色素瘤进展和转移中的染色体 1q ceRNA
  • 批准号:
    10397613
  • 财政年份:
    2021
  • 资助金额:
    $ 23.63万
  • 项目类别:
Chromosome 1q ceRNAs in Melanoma Progression and Metastasis
黑色素瘤进展和转移中的染色体 1q ceRNA
  • 批准号:
    10616492
  • 财政年份:
    2021
  • 资助金额:
    $ 23.63万
  • 项目类别:
BACH2 in Melanoma Development and Resistance
BACH2 在黑色素瘤发展和抵抗中的作用
  • 批准号:
    9329377
  • 财政年份:
    2016
  • 资助金额:
    $ 23.63万
  • 项目类别:
BACH2 in Melanoma Development and Resistance
BACH2 在黑色素瘤发展和抵抗中的作用
  • 批准号:
    8949027
  • 财政年份:
    2016
  • 资助金额:
    $ 23.63万
  • 项目类别:

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