mRNA-Modified FUS/NRF2 Signalling Inhibits Ferroptosis and Promotes Prostate Cancer Growth.

OBJECTIVE

Regarding the imperfect mechanism of occurrence and development of prostate adenocarcinoma (PRAD), this study investigated mRNA-modified FUS/NRF2 signalling to inhibit ferroptosis and promote prostate adenocarcinoma growth.

METHODS

Bioinformatics analysis was used to obtain the expression of FUS and its mRNA modification in PRAD. The expression of FUS in prostate cells (CRPC) and the level of mA methylation modification, ferroptosis (P53 and GPX4), apoptosis (Caspase3), ferroptosis (P53 and GPX4), and apoptosis (Caspase3) in CRPC after ferroptosis inducer Erastin, ferroptosis inhibitor, and FUS knockdown were detected. Autophagy (LC3B), oxidative stress (GSH and ROS), and expression of NRF2/HO-1 pathway are indicators.

RESULTS

FUS was highly expressed in PRAD and phenomenally reduced the survival rate of patients. After knocking down FUS, the level of mA methylation was significantly reduced, and the expressions of ferroptosis markers P53 and GPX4 were phenomenally reduced, while the levels of apoptosis and autophagy markers Caspase3 and LC3B remained unchanged. Upregulated and NRF2/HO-1 pathway indicators were upregulated. It shows that mA methylation modification is reduced when FUS is the low expression, inhibits the expression of P53 and GPX4, downregulates GSH, upregulates ROS, activates the NRF2/HO-1 pathway, and promotes ferroptosis to inhibit the occurrence of RPAD.

CONCLUSIONS

The increase of mA methylation modification can increase the expression of FUS, thereby promoting the expression of P53 and GPX4, upregulating GSH, downregulating ROS, inhibiting the NRF2/HO-1 pathway, inhibiting ferroptosis, and promoting the growth of PRAD.