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.
['Zhu|Kai|K|', 'Li|Ying|Y|', 'Xu|Yikai|Y|']
D000241:Adenosine D000368:Aged D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO D014408:Biomarkers, Tumor D063646:Carcinogenesis D045744:Cell Line, Tumor D002465:Cell Movement D006801:Humans D008297:Male D008875:Middle Aged D009361:Neoplasm Invasiveness D011467:Prostate D011471:Prostatic Neoplasms
FTO Prostate cancer N6-methyladenosine Metastasis