miRNA-34a抑制乳腺癌细胞MCF-7、MDA-MB-231的增殖与侵袭
|
摘要
目的:研究miRNA-34a(miR-34a)对乳腺癌细胞MCF-7、MDA-MB-231的生物调控作用。方法:采用定量PCR检测人乳腺上皮细胞MCF-10A,乳腺癌细胞株MCF-7、T47D、MDA-MB-231、MDAMB-453、Hs578T中miR-34a的表达水平。通过miR-34a mimics分别上调MCF-7、MDA-MB-231细胞中miR-34a的表达水平,MTT和Transwell检测肿瘤细胞增殖能力、侵袭力等生物学行为的变化。结果:乳腺癌细胞MCF-7、T47D、MDA-MB-231、MDA-MB-453、Hs578T中miR-34a处于低表达水平。通过miR-34a mimics上调MCF-7、MDA-MB-231细胞中miR-34a的表达后,细胞的增殖能力被miR-34a抑制(P<0.05),miR-34a对细胞侵袭有显著抑制作用(P<0.05)。结论:miR-34a在乳腺癌细胞MCF-7、T47D、MDA-MB-231、MDA-MB-453及Hs578T中低表达,miR-34a抑制乳腺癌细胞MCF-7、MDA-MB-231的细胞增殖和侵袭能力。
Objective: To identify the regulation function of miRNA-34a( miR-34a) on breast cancer cells MCF-7,MDA-MB-231. Methods: The miR-34 a expression in breast cancer cell line MCF-7,T47D,MDA-MB-231,MDA-MB-453,Hs578 T and breast epithelial cell MCF-10 A were detected by Real-time PCR. The proliferation of MCF-7,MDA-MB-231 cells were detected by MTT method after miR-34a was upregulated. The Transwell chamber was used to investigate the influence of miR-34a on invasion of MCF-7,MDA-MB-231 cells. Results: miR-34 a were in relative downregulated statues in all breast cell lines. The upregulated miR-34 a inhibit MCF-7,MDA-MB-231 cells proliferation( P < 0. 05). The cell invasion ability of MCF-7,MDA-MB-231 cells were suppressed in miR-34a group as well( P < 0. 05). Conclusion: miR-34a is in a relative down expression status in MCF-7,T47D,MDA-MB-231,MDA-MB-453,Hs578 T cells. miR-34a suppresses the breast cancer cell MCF-7,MDA-MB-231 proliferation and invasion in vitro.
Objective: To identify the regulation function of miRNA-34a( miR-34a) on breast cancer cells MCF-7,MDA-MB-231. Methods: The miR-34 a expression in breast cancer cell line MCF-7,T47D,MDA-MB-231,MDA-MB-453,Hs578 T and breast epithelial cell MCF-10 A were detected by Real-time PCR. The proliferation of MCF-7,MDA-MB-231 cells were detected by MTT method after miR-34a was upregulated. The Transwell chamber was used to investigate the influence of miR-34a on invasion of MCF-7,MDA-MB-231 cells. Results: miR-34 a were in relative downregulated statues in all breast cell lines. The upregulated miR-34 a inhibit MCF-7,MDA-MB-231 cells proliferation( P < 0. 05). The cell invasion ability of MCF-7,MDA-MB-231 cells were suppressed in miR-34a group as well( P < 0. 05). Conclusion: miR-34a is in a relative down expression status in MCF-7,T47D,MDA-MB-231,MDA-MB-453,Hs578 T cells. miR-34a suppresses the breast cancer cell MCF-7,MDA-MB-231 proliferation and invasion in vitro.
引文
[1]Siegel RL,Miller KD,Jemal A.Cancer Statistics,2017[J].CA Cancer J Clin,2017,67(1):7-30.
[2]Lin S,Gregory RI.MicroRNA biogenesis pathways in cancer[J].Nat Rev Cancer,2015,15(6):321-333.
[3]Aakula A,Kohonen P,Leivonen SK,et al.Systematic identification of microRNAs that impact on proliferation of prostate cancer cells and display changed expression in tumor tissue[J].Eur Urol,2016,69(6):1120-1128.
[4]Aakula A,Leivonen SK,Hintsanen P,et al.MicroRNA-135b regulates ERalpha,AR and HIF1AN and affects breast and prostate cancer cell growth[J].Mol Oncol,2015,9(7):1287-1300.
[5]Wang R,Ma J,Wu Q,et al.Functional role of miR-34 family in human cancer[J].Curr Drug Targets,2013,14(10):1185-1191.
[6]Adams BD,Parsons C,Slack FJ.The tumor-suppressive and potential therapeutic functions of miR-34a in epithelial carcinomas[J].Expert Opin Ther Targets,2016,20(6):737-753.
[7]Mercey O,Popa A,Cavard A,et al.Characterizing isomiR variants within the microRNA-34/449 family[J].FEBS Lett,2017,591(5):693-705.
[8]Balca-Silva J,Sousa Neves S,Goncalves AC,et al.Effect of miR-34b overexpression on the radiosensitivity of non-small cell lung cancer cell lines[J].Anticancer Res,2012,32(5):1603-1609.
[9]Corney DC,Hwang CI,Matoso A,et al.Frequent downregulation of miR-34 family in human ovarian cancers[J].Clin Cancer Res,2010,16(4):1119-1128.
[10]Daugaard I,Knudsen A,Kjeldsen TE,et al.The association between miR-34 dysregulation and distant metastases formation in lung adenocarcinoma[J].Exp Mol Pathol,2017,102(3):484-491.
[11]Fu J,Qin L,He T,et al.The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis[J].Cell Res,2011,21(2):275-289.
[12]Fu J,Zhang L,He T,et al.TWIST represses estrogen receptoralpha expression by recruiting the NuRD protein complex in breast cancer cells[J].Int J Biol Sci,2012,8(4):522-532.
[13]Zhang L,Yang M,Gan L,et al.DLX4 upregulates TWIST and enhances tumor migration,invasion and metastasis[J].Int J Biol Sci,2012,8(8):1178-1187.
[14]Mudduluru G,Ceppi P,Kumarswamy R,et al.Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer[J].Oncogene,2011,30(25):2888-2899.
[15]Li Z,Luo Q,Xu H,et al.MiR-34b-5p suppresses melanoma differentiation-associated gene 5(MDA5)signaling pathway to promote avian leukosis virus subgroup J(ALV-J)-infected cells proliferaction and ALV-J replication[J].Front Cell Infect Microbiol,2017,7:17.
[16]Leoni G,Tramontano A.A structural view of microRNA-target recognition[J].Nucleic Acids Res,2016,44(9):e82.
[2]Lin S,Gregory RI.MicroRNA biogenesis pathways in cancer[J].Nat Rev Cancer,2015,15(6):321-333.
[3]Aakula A,Kohonen P,Leivonen SK,et al.Systematic identification of microRNAs that impact on proliferation of prostate cancer cells and display changed expression in tumor tissue[J].Eur Urol,2016,69(6):1120-1128.
[4]Aakula A,Leivonen SK,Hintsanen P,et al.MicroRNA-135b regulates ERalpha,AR and HIF1AN and affects breast and prostate cancer cell growth[J].Mol Oncol,2015,9(7):1287-1300.
[5]Wang R,Ma J,Wu Q,et al.Functional role of miR-34 family in human cancer[J].Curr Drug Targets,2013,14(10):1185-1191.
[6]Adams BD,Parsons C,Slack FJ.The tumor-suppressive and potential therapeutic functions of miR-34a in epithelial carcinomas[J].Expert Opin Ther Targets,2016,20(6):737-753.
[7]Mercey O,Popa A,Cavard A,et al.Characterizing isomiR variants within the microRNA-34/449 family[J].FEBS Lett,2017,591(5):693-705.
[8]Balca-Silva J,Sousa Neves S,Goncalves AC,et al.Effect of miR-34b overexpression on the radiosensitivity of non-small cell lung cancer cell lines[J].Anticancer Res,2012,32(5):1603-1609.
[9]Corney DC,Hwang CI,Matoso A,et al.Frequent downregulation of miR-34 family in human ovarian cancers[J].Clin Cancer Res,2010,16(4):1119-1128.
[10]Daugaard I,Knudsen A,Kjeldsen TE,et al.The association between miR-34 dysregulation and distant metastases formation in lung adenocarcinoma[J].Exp Mol Pathol,2017,102(3):484-491.
[11]Fu J,Qin L,He T,et al.The TWIST/Mi2/NuRD protein complex and its essential role in cancer metastasis[J].Cell Res,2011,21(2):275-289.
[12]Fu J,Zhang L,He T,et al.TWIST represses estrogen receptoralpha expression by recruiting the NuRD protein complex in breast cancer cells[J].Int J Biol Sci,2012,8(4):522-532.
[13]Zhang L,Yang M,Gan L,et al.DLX4 upregulates TWIST and enhances tumor migration,invasion and metastasis[J].Int J Biol Sci,2012,8(8):1178-1187.
[14]Mudduluru G,Ceppi P,Kumarswamy R,et al.Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer[J].Oncogene,2011,30(25):2888-2899.
[15]Li Z,Luo Q,Xu H,et al.MiR-34b-5p suppresses melanoma differentiation-associated gene 5(MDA5)signaling pathway to promote avian leukosis virus subgroup J(ALV-J)-infected cells proliferaction and ALV-J replication[J].Front Cell Infect Microbiol,2017,7:17.
[16]Leoni G,Tramontano A.A structural view of microRNA-target recognition[J].Nucleic Acids Res,2016,44(9):e82.