m6A甲基转移酶3在前列腺癌中的表达及其对LNCaP细胞铁死亡的影响

The expressions of m6A methyltransferase-like 3 in prostate cancer and its effect on ferroptosis in LNCaP cells

为探究m6A甲基转移酶3(N6-methyladenosine methyltransferase-like 3,METTL3)在前列腺癌中的表达及其对LNCaP细胞铁死亡的影响,本研究运用UALCAN在线数据库分析了METTL3和SLC7A11在正常前列腺组织和前列腺癌组织中的表达差异及其表达与前列腺癌患者临床病理特征的关系,采用TIMER在线数据库分析了METTL3与铁死亡相关基因SLC7A11表达的相关性。采用实时荧光定量PCR和Western blot检测METTL3 mRNA和蛋白在不同前列腺癌细胞中的表达水平。沉默METTL3的表达后,采用透射电子显微镜观察LNCaP细胞的铁死亡变化,检测SLC7A11的mRNA及蛋白表达情况。UALCAN在线数据库结果显示,METTL3和SLC7A11均高表达于前列腺癌组织,且两者的表达均与前列腺癌患者的Gleason评分、淋巴结转移和TP53突变具有相关性(P<0.05);TIMER分析结果显示,METTL3与铁死亡相关分子SLC7A11的表达呈正相关(P<0.001)。细胞实验结果显示,METTL3在前列腺癌细胞中高表达,而干扰LNCa P细胞METTL3的表达后,细胞铁死亡增加且SLC7A11的表达降低。本研究结果表明,METTL3可能是参与前列腺癌发生铁死亡的重要分子,影响前列腺癌的发生与进展。

This work was aimed to investigate of the expression of N6-methyladenosine methyltransferase-like 3(METTL3)in prostate cancer and its effect on ferroptosis in LNCaP cells.In this study,UALCAN online database was used to analyze the expression of METTL3 and SLC7A11 in normal prostate and prostate cancer tissues,and the relationship of their expression with clinicopathologic features of prostate cancer patients.The correlation of METTL3 with SLC7A11 was evaluated by TIMER database.Moreover,the levels of METTL3 mRNA and protein in different prostate cancer cells were detected by RT-qPCR and Western blot.After the expression of METTL3 was interfered,the ferroptosis of LNCaP cells were evaluated by transmission electron microscopy,and the levels of SLC7A11 m RNA and protein were detected by RT-qPCR and Western blot.The results of UALCAN database showed that METTL3 and SLC7A11 were highly expressed in prostate cancer tissues,and their expression were positively correlated with Gleason score,lymph node metastasis and TP53 mutation of prostate cancer patients(P<0.05).Furthermore,TIMER analysis showed that METTL3 was positively correlated with the expression of ferroptosis molecule SLC7A11(P<0.001).Moreover,the results of cellular experiments showed that METTL3 expression is up-regulated in prostate cancer cells.Interference with METTL3 expression in LNCaP cells increased ferroptosis and decreased the expression of SLC7A11 in prostate cancer cells.This study showed that METTL3 was involved in the occurrence of ferroptosis in prostate cancer,and promoted the occurrence and progression of prostate cancer simultaneously.