FTO modifies the m6A level of MALAT and promotes bladder cancer progression
Le Tao
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorXingyu Mu
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorHaige Chen
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorDi Jin
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorRuiyun Zhang
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorYuyang Zhao
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorJie Fan
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorCorresponding Author
Ming Cao
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Correspondence
Zhihua Zhou, Department of Urology, Menchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Gulou District, Fuzhou 350025, China.
Email: [email protected]
Ming Cao, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Pudong District, Shanghai 200080, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Zhihua Zhou
Department of Urology, Menchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
Correspondence
Zhihua Zhou, Department of Urology, Menchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Gulou District, Fuzhou 350025, China.
Email: [email protected]
Ming Cao, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Pudong District, Shanghai 200080, China.
E-mail: [email protected]
Search for more papers by this authorLe Tao
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorXingyu Mu
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorHaige Chen
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
These authors contributed equally to this work.
Search for more papers by this authorDi Jin
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorRuiyun Zhang
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorYuyang Zhao
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorJie Fan
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Search for more papers by this authorCorresponding Author
Ming Cao
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
Correspondence
Zhihua Zhou, Department of Urology, Menchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Gulou District, Fuzhou 350025, China.
Email: [email protected]
Ming Cao, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Pudong District, Shanghai 200080, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Zhihua Zhou
Department of Urology, Menchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
Correspondence
Zhihua Zhou, Department of Urology, Menchao Hepatobiliary Hospital of Fujian Medical University, 312 Xihong Road, Gulou District, Fuzhou 350025, China.
Email: [email protected]
Ming Cao, Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Pudong District, Shanghai 200080, China.
E-mail: [email protected]
Search for more papers by this authorAbstract
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.
CONFLICT OF INTEREST
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Supporting Information
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