Objective: The aim of the study was to investigate the expression and clinical significance of aldehyde dehydrogenase 1 (ALDH1) in breast cancer patients. Methods: The expression of ALDH1 protein was examined by i...Objective: The aim of the study was to investigate the expression and clinical significance of aldehyde dehydrogenase 1 (ALDH1) in breast cancer patients. Methods: The expression of ALDH1 protein was examined by immunohistochemical staining in 96 breast cancer tissues. The disease-free survival analysis of patients was evaluated based on the clinical follow-up data. Results: Expression of ALDH1 protein had significant correlations with ER, PR, and HER2 proteins (P 〈 0.05), but had no significant correlations with age, tumor size, clinical stage, P-glycoprotein, and lymph node status (P 〉 0.05). The 2-year disease-free survival rate of ALDHl-positive patients was lower than that of ALDHl-negative patients (P 〈 0.05). ALDHl-positive patients undergoing chemotherapy and hormonal therapy had lower 2-year disease-free survival rate than ALDHl-negative patients (P 〈 0.05). Conclusion: ALDH1 expression might play an important role in drug resistant, and ALDH1 may be used as a prognostic marker.展开更多
ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological processes.Here,we show that ALKBH5 is required for breast tumor growth.Interestingly,PRMT6 directly met...ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological processes.Here,we show that ALKBH5 is required for breast tumor growth.Interestingly,PRMT6 directly methylates ALKBH5 at R283,which subsequently promotes breast tumor growth.Furthermore,arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation,leading to increased aerobic glycolysis.Moreover,PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout mice.Collectively,these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.展开更多
文摘Objective: The aim of the study was to investigate the expression and clinical significance of aldehyde dehydrogenase 1 (ALDH1) in breast cancer patients. Methods: The expression of ALDH1 protein was examined by immunohistochemical staining in 96 breast cancer tissues. The disease-free survival analysis of patients was evaluated based on the clinical follow-up data. Results: Expression of ALDH1 protein had significant correlations with ER, PR, and HER2 proteins (P 〈 0.05), but had no significant correlations with age, tumor size, clinical stage, P-glycoprotein, and lymph node status (P 〉 0.05). The 2-year disease-free survival rate of ALDHl-positive patients was lower than that of ALDHl-negative patients (P 〈 0.05). ALDHl-positive patients undergoing chemotherapy and hormonal therapy had lower 2-year disease-free survival rate than ALDHl-negative patients (P 〈 0.05). Conclusion: ALDH1 expression might play an important role in drug resistant, and ALDH1 may be used as a prognostic marker.
基金supported by research grants from National Natural Science Foundation of China(Nos.81972489 and 82003201)National Natural Science Foundation of Shandong Province(Nos.ZR2020YQ58 and ZR2020QH255)+1 种基金Shandong Province College Science and Technology Plan Project(No.J17KA254)Projects of medical and health technology development program in Shandong Province(No.2018WS057).
文摘ALKBH5 is a master regulator of N6-methyladenosine(m6A)modification,which plays a crucial role in many biological processes.Here,we show that ALKBH5 is required for breast tumor growth.Interestingly,PRMT6 directly methylates ALKBH5 at R283,which subsequently promotes breast tumor growth.Furthermore,arginine methylation of ALKBH5 by PRMT6 increases LDHA RNA stability via m6A demethylation,leading to increased aerobic glycolysis.Moreover,PRMT6-mediated ALKBH5 arginine methylation is confirmed in PRMT6-knockout mice.Collectively,these findings identify a PRMT6-ALKBH5-LDHA signaling axis as a novel target for the treatment of breast cancer.