摘要
目的:探讨线粒体裂变调节因子1(MTFR1)介导的线粒体分裂参与结肠癌恶性生物学行为的机制。方法:使用Gepia数据库分析结肠癌MTFR1表达情况,及其与结肠癌预后之间的关联。将人结肠癌细胞系Lovo细胞分为载体组(Vector)和MTFR1过表达质粒组(MTFR1)或MTFR1敲低组(sh-MTFR1)及对照组(sh-NC)。采用实时定量PCR检测细胞中MTFR1。通过Transwell试验评估细胞迁移,和MitoTracker Red染色检测细胞中线粒体互连性。通过Western blotting检测细胞ERK1/2和过氧化物酶体增殖物激活受体γ共激活因子1-α(PGC-1α)蛋白表达。结果:Gepia分析显示,在结肠腺癌组织中观察到更高的MTFR1 RNA表达水平(P<0.01),并且MTFR1表达水平升高预示结肠腺癌病人预后较差(P<0.01)。与Vector组细胞相比,MTFR1组Lovo细胞转移和侵袭细胞数显著增加(P<0.01和P<0.05),线粒体分支长度减少(P<0.05)。与sh-NC组相比,sh-MTFR1组Lovo细胞转移和侵袭细胞数均明显减少(P<0.01),线粒体分支长度增加(P<0.05)。与Vector组相比,MTFR1组细胞中p-ERK1/2和PGC-1α均上调(P<0.05)。随着PD0325901浓度的增加,在过表达MTFR1的Lovo细胞中观察到p-ERK1/2磷酸化依赖性抑制(P<0.01),PGC-1α逐渐减少(P<0.01)。结论:MTFR1介导的线粒体分裂参与结肠癌恶性生物学行为,这种效应至少部分归因于ERK1/2-PGC-1α途径激活。
Objective:To explore the mechanism of mitochondrial fission regulator 1(MTFR1)-mediated mitochondrial fission involved in the malignant biological behavior of colon cancer.Methods:The expression of MTFR1 in colon cancer and its association with colon cancer prognosis were analyzed using the Gepia database.The human colon cancer cell line Lovo cells were divided into vector group(Vector),MTFR1 overexpression plasmid group(MTFR1)or MTFR1 knockdown group(sh-MTFR1),and control group(sh-NC).MTFR1 in cells was detected by quantitative real-time PCR.Cell migration was assessed by Transwell assay,and mitochondrial interconnectivity in cells was detected by MitoTracker Red staining.The protein expressions of ERK1/2 and peroxisome proliferator-activated receptor gamma coactivator 1-α(PGC-1α)were detected by Western blotting.Results:Gepia analysis showed that higher MTFR1 RNA expression levels were observed in colon adenocarcinoma tissues(P<0.01),and elevated MTFR1 expression levels predicted poor prognosis in colon adenocarcinoma patients(P<0.01).Compared with the Vector group,the number of Lovo cell metastasis and invasion in the MTFR1 group increased significantly(P<0.01 and P<0.05)and the length of mitochondrial branches decreased significantly(P<0.05).Compared with sh-NC group,the number of Lovo cell metastasis and invasion in sh-MTFR1 group decreased significantly(P<0.01)and the length of mitochondrial branch increased significantly(P<0.05).In addition,compared with the Vector group,both p-ERK1/2 and PGC-1αwere up-regulated in the MTFR1 group(P<0.05).With increasing concentration of PD0325901,phosphorylation-dependent inhibition of p-ERK1/2(P<0.01),and PGC-1αgradual decrease(P<0.01)were observed in Lovo cells overexpressing MTFR1.Conclusions:MTFR1-mediated mitochondrial fission is involved in the malignant biological behavior of colon cancer.This effect is attributed at least in part to ERK1/2-PGC-1αpathway activation.
作者
吴铃
鲍峰
于颖娟
WU Ling;BAO Feng;YU Yingjuan(Department of Surgery,Sichuan College of Traditional Chinese Medicine,Mianyang Sichuan 621000;Department of General Surgery,Mianyang Central Hospital,Mianyang Sichuan 621000,China)
出处
《蚌埠医学院学报》
2024年第12期1562-1566,1572,共6页
Journal of Bengbu Medical College
基金
四川省卫生健康科研基金项目(20210914)。
关键词
结肠肿瘤
线粒体裂变调节因子1
线粒体分裂
转移
colonic neoplasms
mitochondrial fission regulator 1
mitochondrial fission
metastasis
