FTO modifies the m6A level of MALAT and promotes bladder cancer progression

• Published in: Clinical and translational medicine 2021-02, Vol.11 (2), p.e310-n/a
• Main Authors: Tao, Le, Mu, Xingyu, Chen, Haige, Jin, Di, Zhang, Ruiyun, Zhao, Yuyang, Fan, Jie, Cao, Ming, Zhou, Zhihua
• Format: Article
• Language: English
• Subjects: Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism; Biomarkers; Bladder cancer; Cell growth; cell viability; Clinical medicine; Cohort Studies; Disease Progression; Female; FTO; Gene expression; Humans; Lung cancer; MAL2; MALAT1; Male; Medical prognosis; Metabolism; Metastasis; Middle Aged; miR‐384; Myelin and Lymphocyte-Associated Proteolipid Proteins - genetics; Myelin and Lymphocyte-Associated Proteolipid Proteins - metabolism; N6‐methyladenosine mRNA modification; Pathogenesis; Prognosis; Proteins; Reagents; tumor growth; Tumorigenesis; Urinary Bladder - metabolism; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism
• ISSN: 2001-1326; 2001-1326
• DOI: 10.1002/ctm2.310

Background Nearly a half million people around the world are diagnosed with bladder cancer each year, and an incomplete understanding of its pathogenicity and lack of efficient biomarkers having been discovered lead to poor clinical management of bladder cancer. Fat mass and obesity‐associated protein (FTO) is a critical player in carcinogenesis. We, here, explored the role of FTO and unraveled the mechanism of its function in bladder cancer. Methods Identification of the correlation of FTO with bladder cancer was based on both bioinformatics and clinical analysis of tissue samples collected from a cohort of patients at a hospital and microarray data. Gain‐of‐function and loss‐of‐function assays were conducted in vivo and in vitro to assess the effect of FTO on bladder carcinoma tumor growth and its impact on the bladder carcinoma cell viability. Moreover, the interactions of intermediate products were also investigated to elucidate the mechanisms of FTO function. Results Bladder tumor tissues had increased FTO expression which correlated with clinical bladder cancer prognosis and outcomes. Both in vivo and in vitro, it played the function of an oncogene in stimulating the cell viability and tumorigenicity of bladder cancer. Furthermore, FTO catalyzed metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) demethylation, regulated microRNA miR‐384 and mal T cell differentiation protein 2 (MAL2) expression, and modulated the interactions among these processes. Conclusions The interplay of these four clinically relevant factors contributes to the oncogenesis of bladder cancer. FTO facilitates the tumorigenesis of bladder cancer through regulating the MALAT/miR‐384/MAL2 axis in m6A RNA modification manner, which ensures the potential of FTO for serving as a diagnostic or prognostic biomarker in bladder cancer. FTO stimulates tumor growth of bladder cancer through regulating MALAT1 methylation. MALAT1 and MAL2 interact with miR‐384 for regulating tumor growth of bladder cancer. FTO promotes bladder cancer tumor growth via MALAT1/miR‐384/MAL2 axis.