Abstract:Objective To study the effect and mechanism of miR-133a on inhibiting osteosarcoma cell invasion via targeting matrix metalloproteinase-14 (MMP-14). Methods Normal osteoblasts hFOB1.19 and osteosarcoma cells MG63,U2OS and SAOS2 were cultured and the expression of miR-133a was detected by fluorescence quantitative PCR.MG63 cells were divided into miR-negative control (NC) group,miR-133a group,pcDNA3.1+miR-NC group,pcDNA3.1+miR-133a group,pcDNA3.1-MMP-14+miR-133a group and transfected with NC mimic,miR-133a mimic,pcDNA3.1 plasmid and MMP-14 overexpressed pcDNA3.1 plasmid.Thenthe number of cell invasion was detected by Transwell,the expression level of MMP-14 was detected by Western blot and the targeted binding of miR-133a to 3'UTR of MMP-14 gene mRNA was verified by double luciferase reporter gene assay.Results The expression level of miR133a in MG63,U2OS and SAOS2 cells were lower than that in hFOB1.19 cell,and the expression level of miR-133a in MG63 cells decreased most significantly.The invasion number of MG63 cells in miR-133a group was less than that in miR-NC group.The expression level of MMP-14 and the fluorescence activity of double luciferase reporter gene containing wild type 3'UTR of MMP-14 were lower than those in miR-NC group.The invasion number of MG63 cells in pcDNA3.1-MMP-14+miR-133a group was more than that in pcDNA3.1+miR-133a group.Conclusion miR-133a can inhibit the invasion of osteosarcoma MG63 cells,and the targeted inhibition of MMP-14 geneis one of the possible molecular mechanism.
[1]王文剑,于秀淳,韩加,等.1593例骨肉瘤流行病及治疗的回顾性分析[J].中华骨科杂志,2018,38(18):1097-1107.
[2]吴志明,刘江涛,徐俊昌,等.miR133 a和miR539在骨肉瘤组织中的表达及其与临床病理特征和预后的相关性分析[J].解放军医药杂志,2019,31(4):32-36.
[3]Shen Y,Yang Y,Li Y.MiR-133a acts as a tumor suppressor in lung cancer progression by regulating the LASP1 and TGF-beta/Smad3 signaling pathway[J].Thorac Cancer,2020,11(12):3473-3481.
[4]Han S,Ding X,Wang S,et al.MiR-133a-3p regulates hepatocellular carcinoma progression through targeting CORO1C[J].Cancer Manag Res,2020,21(12):8685-8693.
[5]Arámbula-Meraz E,Bergez-Hernández F,Leal-León E,et al.Expression of miR-148b-3p is correlated with overexpression of biomarkers in prostate cancer[J].Genet Mol Biol,2020,43(1):e20180330.
[6]Wang H,Zhang Y,Zhang Y,et al.Cryptotanshinone inhibits lung cancer invasion via microRNA-133a/matrix metalloproteinase 14 regulation[J].Oncol Lett,2019,18(3):2554-2559.
[7]张建业,张卫华.miR96干扰NKD2表达对骨肉瘤MG63细胞株的增殖、凋亡的影响[J].实用骨科杂志,2021,27(7):615-618;631.
[8]Tian BG,Hua Z,Wang ZJ,et al.Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis[J].Eur Rev Med PharmacolSci,2020,24(3):1030-1040.
[9]Wang Y,Yang J,Chen P,et al.MicroRNA-320a inhibits invasion and metastasis in osteosarcoma by targeting cytoplasmicpolyadenylation element-binding protein 1[J].Cancer Med,2020,9(8):2833-2845.
[10]Bitaraf A,Babashah S.Aberrant expression of a five-microRNA signature in breast carcinoma as a promising biomarker for diagnosis[J].J Clin Lab Anal,2020,34(2):e23063.
[11]Lim JH,Kim SG,Choi JM,et al.helicobacter pylori is associated with mir-133a expression through promoter methylation in gastric carcinogenesis[J].Gut Liver,2018,12(1):58-66.
[12]Tang Y,Pan J,Huang S,et al.Downregulation of miR-133a-3p promotes prostate cancer bone metastasis via activating PI3K/AKT signaling[J].J Exp Clin Cancer Res,2018,37(1):160.
[13]Li B,Lou G,Zhou J.MT1MMP promotes the proliferation and invasion of gastric carcinoma cells via regulating vimentin and Ecadherin[J].Mol Med Rep,2019,19(4):2519-2526.
[14]Li M,Ren CX,Zhang JM,et al.The effects of miR-195-5p/MMP-14 on proliferation and invasion of cervical carcinoma cells through tnf signaling pathway based on bioinformatics analysis of microarray profiling[J].Cell Physiol Biochem,2018,50(4):1398-1413.
[15]SuetsuguT,KoshizukaK,SekiN,etal.Downregulation of matrix metalloproteinase 14 by the antitumor miRNA,miR-150-5p,inhibits the aggressiveness of lung squamous cell carcinoma cells[J].Int J Oncol,2018,52(3):913-924.
[16]Ho XD,Phung P,Q LeV,et al.Whole transcriptome analysis identifies differentially regulated networks between osteosarcoma and normal bone samples[J].ExpBiol Med (Maywood),2017,242(18):1802-1811.
[17]Wu D,ChenK,BaiY,etal.Screening of diagnostic markers for osteosarcoma[J].Mol Med Rep,2014,10(5):2415-2420.