ABSTRACT
AMP-activated protein kinase(AMPK)is a conserved cellular energy receptor that plays an important role in regulating cell growth,proliferation,differentiation,autophagy,phosphorylation,crosstalk,and glucose and lipid metabolism.AMPK is activated during low-energy or other extreme conditions,and it is suppressed by an excess of nutrients to maintain the energy balance.Additionally,the regulatory mechanism of the AMPK signaling pathway mediating ferroptosis reflects its unique role.AMPK plays a specialized regulatory function in various organelles,which provides a new direction for disease therapy.It is also a therapeutic target to prevent diseases such as reproductive system diseases,aging,cancer,inflammation and cardiac dysfunction.This article reviews cellular energy imbalance.AMPK stimulates its potential therapeutic potential in diseases and drugs through diverse signal regulatory mechanisms.It provides a new treatment for different system diseases.This review summarizes the diverse regulatory mechanisms of the AMPK signaling pathway and provides a theoretical reference for cancer therapy and other disease therapies targeting AMPK.
ABSTRACT
Objective To explore the relationship between m6A RNA methylation regulators and prognosis of prostate cancer.Methods Clinicopathological and mRNA-related data of 496 cases of prostate cancer were downloaded from the Cancer Genome Atlas(TCGA)database,and 12 m6A regulators were identified:METTL3,METTL14,WTAP,RBM15,ZC3H13,YTHDC1,YTHDC2,YTHDF1,YTHDF2,HNRNPC,FTO,and ALKBH5.The m6A regulators differentially expressed in prostate cancer samples were screened.Unsupervised clustering of prostate cancer tissues was used to compare differences in overall survival.Multivariate Cox regres-sion analysis was used to divide patients into high-and low-risk groups according to the risk scores,and survival rates were compared.The risk score of clinicopathological factors was determined,and a multivariate Cox regression analysis model was constructed to evaluate the prognostic prediction value.Immunohistochemical staining was performed to detect METTL14 and FTO expression in prostate cancer tis-sues.Results Eight differentially expressed regulators were screened from 12 m6A regulators.Unsupervised cluster analysis divided the samples into Clusters 1,2,and 3 and found significant differences in survival time in all three groups.Multivariate Cox regression analyses revealed that METTL14and FTOwere strongly associated with the prognosis of patients with prostate cancer.A Cox regression model con-structed to score the risk of prostate cancer revealed that the high-and low-risk groups had survival differences,and the risk score could be used as an independent prognostic factor.The positive expression rates of METTL14 and FTO protein in prostate cancer tissues were significantly higher than those in adjacent tissues(P<0.05).Conclusion In this study,a prognostic prediction model based on m6A regulators of prostate cancer was constructed,in which the risk score could be used as an independent prognostic factor.METTL14and FTOcould be used as molecular markers for the diagnosis of prostate cancer and as potential targets for treatment.