The FTO m6A demethylase inhibits the invasion and migration of prostate cancer cells by regulating total m6A levels

Aims: N6-Methyladenosine (m⁶A) is the most frequent posttranscriptional modification and plays important roles in tumorigenesis and metastasis. The roles of fat mass and obesity-associated (FTO) in metabolic diseases have been widely explored. However, the molecular mechanisms and physiological functions of FTO in prostate Cancer remain largely unknown. This study aimed to explore the exact functions of FTO in the progression of prostate Cancer metastasis.

Main methods: Dot blot and m⁶A RNA methylation quantification assays were performed to determine m⁶A levels. The protein and mRNA expression levels were detected using immunoblot (IB) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Cell invasion and migration abilities were measured using transwell and wound healing assays. Bioinformatics was used to measure the expression level of FTO and possible correlation between FTO levels and advanced tumor stage. Immunofluorescence (IF) was performed to measure the cellular localization of FTO.

Key findings: FTO was downregulated in prostate Cancer tissues and cell lines, and the m⁶A content was increased. Importantly, patients with lower FTO expression had advanced tumor stage and higher Gleason scores. Gain- and loss-of-function assays revealed that FTO inhibits prostate Cancer cell invasion and migration in vitro. Moreover, we confirmed that FTO can decrease the total m⁶A level.

Significance: The present study revealed that the FTO m⁶A demethylase inhibits prostate Cancer cell invasion and migration by regulating total m⁶A levels.