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The m6A demethylase FTO targets POLQ to promote ccRCC cell proliferation and genome stability maintenance.
He, Yichen; Chen, Yimeng; Li, Zhengsheng; Wu, Changping.
Afiliación
  • He Y; Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
  • Chen Y; Institute of Cell Therapy, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
  • Li Z; Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
  • Wu C; Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, China.
J Cancer Res Clin Oncol ; 150(2): 30, 2024 Jan 25.
Article en En | MEDLINE | ID: mdl-38270643
ABSTRACT
BACKGROUND AND

AIM:

As the first identified m6A demethylase, FTO has been implicated in the progression of various cancers. However, the specific mechanism of FTO in clear cell renal cell carcinoma (ccRCC) remains incompletely understood. In this study, we aimed to explore the potential molecular mechanisms influencing the progression of ccRCC.

METHODS:

We initially assessed the expression of FTO in tumor and adjacent tissues using TCGA database, RT-qPCR, and Western blot. We then conducted CCK-8, cell cycle analysis, and colony formation assay to investigate the impact of FTO on ccRCC cell proliferation. MeRIP-seq and RNA-seq were employed to identify potential downstream targets of FTO in ccRCC, and these findings were further validated through dual-luciferase reporter assays and MeRIP-qPCR. Then, DNA damage and cell death were assessed separately through gammaH2AX immunofluorescence detection and the LIVE/DEAD Fixable Dead Cell Stain assay, respectively. Subsequently, we identified downstream pathways influenced by FTO's regulation of POLQ through TCGA database analysis and GSEA enrichment analysis. Validation was carried out through Western blot.

RESULTS:

FTO is highly expressed in ccRCC tissues and cell lines. Furthermore, ROC curve demonstrates that FTO contributes to the diagnosis of ccRCC. FTO modulates m6A modification, consequently influencing the expression of POLQ, thus facilitating cell proliferation and maintaining genome stability in ccRCC.

CONCLUSION:

FTO could potentially serve as a diagnostic marker for ccRCC. FTO promotes the progression of ccRCC by regulating m6A modification, making the inhibition of FTO a potential novel therapeutic strategy in ccRCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma / Carcinoma de Células Renales / Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato / ADN Polimerasa theta / Neoplasias Renales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Cancer Res Clin Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma / Carcinoma de Células Renales / Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato / ADN Polimerasa theta / Neoplasias Renales Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Cancer Res Clin Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania