The abundant and reversible N6‐methyladenosine (m6A) R NA modification and its modulators have important roles in regulating various gene expression and biological processes. Here, we demonstrate that fat mass and obesity associated ( FTO ), as an m6A demethylase, plays a critical anti‐tumorigenic role in clear cell renal cell carcinoma (cc RCC ). FTO is suppressed in cc RCC tissue. The low expression of FTO in human cc RCC correlates with increased tumour severity and poor patient survival. The Von Hippel‐Lindau‐deficient cells expressing FTO restores mitochondrial activity, induces oxidative stress and ROS production and shows impaired tumour growth, through increasing expression of PGC ‐1α by reducing m6A levels in its mRNA transcripts. Our work demonstrates the functional importance of the m6A methylation and its modulator, and uncovers a critical FTO ‐ PGC ‐1α axis for developing effective therapeutic strategies in the treatment of cc RCC .

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Circular RNAs (circRNAs), one kind of non-coding RNA, have been reported as critical regulators for modulating gene expression in cancer. In this study, microarray analysis was used to screen circRNA expression profiles of bladder cancer (BC) 5637 cells, T24 cells and normal control SV-HUC-1 cells. The data from the microarray showed that hsa_circ_0075828 (named circCASC15) was most highly expressed in 5637 and T24 cells. circCASC15 was highly expressed in BC tissues and cells. Overexpression of circCASC15 was closely associated with BC tumor stage and promoted cell proliferation significantly in vitro and in vivo. Mechanistically, circCASC15 could act as miR-1224-5p sponge to activate the expression of CREB1 to promote cell proliferation in BC. In short, circCASC15 promotes cell proliferation in BC, which might be a new molecular target for BC diagnosis and therapy. [BMB Reports 2020; 53(2): 82-87] BMB Rep. 2020; 53(2): 82-87 www.bmbreports.org hsa_circ_0075828 promotes proliferation in BC Chengle Zhuang, et al.