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N6-methyladenosine (m6A) methylation participates in the progression of bladder cancer (BCa). Nevertheless, the regulatory mechanism of alpha-ketoglutarate-dependent dioxygenase FTO influencing the BCa progression has still remained elusive. In this study, to investigate the tumor-suppressive effects of FTO via m6A RNA methylation on BCa patients, a total of 15 cancer tissues and adjacent normal tissues (ANTs) were collected from BCa patients who received tumor resection in our hospital from September 2015 to December 2019. We found that the FTO expression was significantly reduced in cancer tissues compared with that in ANTs, which indicated a lower malignant potential and a higher overall survival rate. It was revealed that overexpression of FTO in two human urinary BCa cell lines (HT-1197 and HT-1376) significantly decreased the cell proliferation and invasion abilities compared with the negative controls, whereas the cell apoptosis was markedly enhanced. In addition, we noted that the changes in m6A methylation level mainly appeared at 5ʹ untranslated region (5ʹ UTR) of MALAT1 and NOTCH1 transcripts, and at 3ʹ UTR of CSNK2A2 and ITGA6 transcripts, responding to the overexpression of FTO. Mechanistically, we found that the splicing factor, proline- and glutamine-rich (SFPQ) could influence the FTO-mediated m6A RNA demethylation, eventually affecting the gene expression. This study provided a new insight into the relationship between the FTO expression and the m6A RNA methylation, assisting scholars to better understand the pathogenesis of BCa.

MicroRNA-148a (miR-148a) has been reported to be deregulated in different tumor types, whereas the biological function of miR-148a in renal cell carcinoma (RCC) largely remains unexplored. In the present study we investigated the clinical significance, biological effects, and the underlying molecular mechanisms of miR-148 in RCC. Here, we showed that miR-148a was significantly downregulated in RCC tissues and cell lines. Low expression of miR-148a in RCC tissues was associated with large tumor size, advanced TNM stage, and lymph node metastasis. Functional assays revealed that overexpression of miR-148a significantly inhibited RCC cell proliferation, colony formation, migration and invasion in vitro and suppressed RCC xenograft tumor growth in vivo. In addition, using quantitative RT-PCR (qRT-PCR), western blot analysis and luciferase reporter assays, AKT2 was confirmed to be a direct target of miR-148a. AKT2 expression was upregulated, and was negatively correlated with miR-148a expression in RCC tissues (r=-0.641, P