MiR-514与胃癌细胞凋亡的关系及机制
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摘要
目的探讨微小RNA-514(microRNA-514,miR-514)与胃癌细胞凋亡的关系及机制。方法实时定量PCR检测80例胃癌组织及癌旁正常胃黏膜组织中miR-514的表达情况,分析miR-514与患者各病理参数之间的关系。应用miR-514模拟物转染人胃癌细胞株MGC803,检测转染前后细胞凋亡率及凋亡相关基因的情况。结果胃癌组织中miR-514水平(0. 3619±0. 2103)明显低于癌旁正常胃黏膜(0. 6943±0. 3032)(t=-8. 0573; P<0. 001); miR-514表达与肿瘤的淋巴结转移有关(t=-2. 5620,P=0. 012 3); miR-514模拟物转染人胃癌细胞株MGC803后细胞的活性明显降低而凋亡率明显增高(P<0. 05);转染后凋亡相关基因Bcl-2、x IAP的mRNA和蛋白表达明显降低,而Bax的mRNA和蛋白表达明显增高(P <0. 05)。结论胃癌组织中miR-514的表达减弱,miR-514可能通过调节一些凋亡基因表达而参与肿瘤的凋亡过程。
Objective To investigate the relationship between microRNA-514( miR-514)and apoptosis of gastric cancer and related mechanism. Methods Expression of miR-514 in gastric cancer tissues and cancer-adjacent normal tissues from 80 patients were detected with real-time PCR,and relationship between miR-514 and clinicopathological parameters was investigated. miR-514 mimics was utilized to transfected into gastric cancer cell line MGC803,then variation of apoptosis rate and related genes was detected. Results Level of miR-514 was lower in gastric cancer tissues( 0. 3619 ± 0. 2103) than that in cancer-adjacent normal tissues( 0. 6943 ± 0. 3032)( t =-8. 0573,P < 0. 001). Expression of miR-514 was related with lymph node metastasis( t =-2. 5620,P = 0. 0123). After transfection of miR-514 mimics,cell activity was decreased,while apoptotic rate of MGC803 increased significantly( P < 0. 05); mRNA and protein of Bcl-2,xIAP were decreased significantly,while Bax increased significantly( P<0. 05). Conclusion Reduction of miR-514 existed in gastric cancer tissues,which may be invovled in apoptosis of gastric cancer cells by regulating apoptosis related genes.
Objective To investigate the relationship between microRNA-514( miR-514)and apoptosis of gastric cancer and related mechanism. Methods Expression of miR-514 in gastric cancer tissues and cancer-adjacent normal tissues from 80 patients were detected with real-time PCR,and relationship between miR-514 and clinicopathological parameters was investigated. miR-514 mimics was utilized to transfected into gastric cancer cell line MGC803,then variation of apoptosis rate and related genes was detected. Results Level of miR-514 was lower in gastric cancer tissues( 0. 3619 ± 0. 2103) than that in cancer-adjacent normal tissues( 0. 6943 ± 0. 3032)( t =-8. 0573,P < 0. 001). Expression of miR-514 was related with lymph node metastasis( t =-2. 5620,P = 0. 0123). After transfection of miR-514 mimics,cell activity was decreased,while apoptotic rate of MGC803 increased significantly( P < 0. 05); mRNA and protein of Bcl-2,xIAP were decreased significantly,while Bax increased significantly( P<0. 05). Conclusion Reduction of miR-514 existed in gastric cancer tissues,which may be invovled in apoptosis of gastric cancer cells by regulating apoptosis related genes.
引文
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[3] Yang AJ,Wang M,Wang Y,et al.Cancer cell-derived von Willebrand factor enhanced metastasis of gastric adenocarcinoma[J].Oncogenesis,2018,7(1):12.
[4] Fang S,Hong H,Li L,et al. Plasminogen kringle 5 suppresses gastric cancer via regulating HIF-1αand GRP78[J].Cell Death Dis,2017,8(10):e3144.
[5] Xu L,Zhang Y,Qu X,et al. DR5-Cbl-b/c-Cbl-TRAF2complex inhibits TRAIL-induced apoptosis by promoting TRAF2-mediated polyubiquitination of caspase-8 in gastric cancer cells[J].Mol Oncol,2017,11(12):1733-1751.
[6] Kasiappan R,Rajarajan D.Role of MicroRNA regulation in obesity-associated breast cancer:nutritional perspectives[J].Adv Nutr,2017,8(6):868-888.
[7] Jin Y,Tao LP,Yao SC,et al. MicroRNA-582-5p suppressed gastric cancer cell proliferation via targeting AKT3[J].Eur Rev Med Pharmacol Sci,2017,21(22):5112-5120.
[8] Fan L,Tan B,Li Y,et al.Upregulation of miR-185 promotes apoptosis of the human gastric cancer cell line MGC803[J].Mol Med Rep,2018,17(2):3115-3122.
[9] Feng A,Yuan X,Li X.MicroRNA-345 inhibits metastasis and epithelial-mesenchymal transition of gastric cancer by targeting FOXQ1[J].Oncol Rep,2017,38(5):2752-2760.
[10]杨媛慧,路瑞静,杨会林,等.miR-514在肾癌中的异常表达及其临床意义[J].中国实验诊断学,2015,19(6):933-936.
[11] Yang L.Incidence and mortality of gastric cancer in China[J].World J Gastroenterol,2006,12(1):17-20.
[12] Chen W,Zheng R,Zhang S,et al. Report of cancer incidence and mortality in China,2010[J].Ann Transl Med,2014,2(7):61.
[13] Curea FG,Hebbar M,Ilie SM,et al.Current targeted therapies in HER2-positive gastric adenocarcinoma[J].Cancer Biother Radiopharm,2017,32(10):351-363.
[14] Klameth L,Rath B,Hamilton G.In vitro cytotoxic activities of the oral platinum(Ⅳ)prodrug oxoplatin and HSP90inhibitor ganetespib against a panel of gastric cancer cell lines[J].J Cancer,2017,8(10):1733-1743.
[15] Wald P,Liu XS,Pettit C,et al.Prognostic value of microRNA expression levels in pancreatic adenocarcinoma:a review of the literature[J]. Oncotarget,2017,8(42):73345-73361.
[16] Du X,Liu B,Luan X,et al.miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy[J].Exp Ther Med,2018,15(1):599-605.
[17] Yang H,Wang L,Tang X,et al.miR-203a suppresses cell proliferation by targeting E2F transcription factor 3 in human gastric cancer[J]. Oncol Lett,2017,14(6):7687-7690.
[18] Guan H,Li W,Li Y,et al.MicroRNA-93 promotes proliferation and metastasis of gastric cancer via targeting TIMP2[J].PLoS One,2017,12(12):e0189490.
[19] Wotschofsky Z,Busch J,Jung M,et al. Diagnostic and prognostic potential of differentially expressed miRNAs between metastatic and non-metastatic renal cell carcinoma at the time of nephrectomy[J]. Clin Chim Acta,2013,416:5-10.
[20] Pihán P,Carreras-Sureda A,Hetz C. BCL-2 family:integrating stress responses at the ER to control cell demise[J].Cell Death Differ,2017,24(9):1478-1487.
[21] Daniel C,Mato AR.BCL-2 as a therapeutic target in chronic lymphocytic leukemia[J]. Clin Adv Hematol Oncol,2017,15(3):210-218.
[22] Liu Z,Ding Y,Ye N,et al.Direct activation of Bax protein for cancer therapy[J].Med Res Rev,2016,36(2):313-341.
[23] Chaudhary AK,Yadav N,Bhat TA,et al.A potential role of X-linked inhibitor of apoptosis protein in mitochondrial membrane permeabilization and its implication in cancer therapy[J]. Drug Discov Today,2016,21(1):38-47.