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

Abstract

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.

A new m6A methylation-related gene signature for prognostic value in patient with urothelial carcinoma of the bladder

“…Wen et al found that knockdown of FTO apparently induces BC cell proliferation and migration, and the effect of cisplatin-induced cytotoxicity of BC cell is rescued via the inhibition of FTO [40]. In addition, FTO can demethylate MALAT1 which further promote BC cell viability and proliferation through the miR-384/MAL2 m 6 A axis [41]. Similarly, Song et al revealed that FTO, stabilized by USP-18 via inhibition of proteasomal degradation, reduces PYCR1 m 6 A methylation and stabilizes its transcript, which finally facilitates BC cell initiation and progression [42].…”

m6A demethylase FTO induces NELL2 expression by inhibiting E2F1 m6A modification leading to metastasis of non-small cell lung cancer

“… 17 Due to its role in cellular metabolism, FTO has thus been considered as a promising factor involved in the pathogenesis of various cancers through inducing tumorigenesis and chemoresistance. 18 , 19 Although the expression of FTO has been found to be upregulated in NSCLC, 20 there is limited knowledge regarding the specific mechanism of FTO in NSCLC. On the basis of aforementioned evidence, we proposed a hypothesis that the FTO/E2F1/NELL2 axis may confer tumor-supporting roles in the cell behavior of NSCLC cells and thus accelerate NSCLC progression.…”

m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma

“…For example, M6A methyltransferase METTL3 is upregulated in melanoma and modulates melanoma cell invasiveness through MMP2 (Dahal et al, 2019). FTO can promote bladder cancer by regulating the miR-384, MALAT, MAL2 axis through m6A modifications (Tao et al, 2021). The IGF2BP2, LINC00460, and DHX9 complex could promote colorectal cancer proliferation and metastasis by mediating the stability of HMGA1 (Hou et al, 2021).…”