乳腺癌中靶向抑制REST协阻抑制因子3表达的微小RNA的预测及其高通量数据验证
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摘要
目的预测并采用高通量数据验证乳腺癌中靶向抑制REST协阻抑制因子3(RCOR3)基因表达的微小RNA(miRNA)。方法分别利用RNA22、miRanda、PicTar、TargetScan和PITA 5种不同软件预测靶向抑制RCOR3基因表达的miRNA,然后取其交集。通过高通量数据验证所获miRNA对RCOR3表达的负向调控作用,并经泛癌症分析进一步验证miRNA对RCOR3表达的抑制作用。结果取交集后得到miRNA-128-3p、miRNA-27a、miRNA-27b和miRNA-19b-3p。乳腺癌中miRNA-128-3p、miRNA-27a、miRNA-27b及miRNA-19b-3p与RCOR3基因表达水平均呈负相关(P <0. 05)。泛癌症分析结果显示,结直肠腺癌、肺腺癌、肾透明细胞癌和子宫内膜癌中miRNA-128-3p与RCOR3基因表达均呈负相关(均P <0. 05),结直肠腺癌、膀胱尿路上皮癌、肺腺癌、肺鳞癌、肾透明细胞癌、子宫内膜癌和急性髓性白血病中miRNA-27a与RCOR3基因的表达均呈负相关(均P <0. 05)。结论乳腺癌中miRNA-128-3p和miRNA-27a、miRNA-27b及miRNA-19b-3p具有潜在的靶向抑制RCOR3表达的功能。
Objective To predict and validate by high-throughput data the micro RNA( miRNA) targetedly inhibiting REST corepressor 3( RCOR3) expression in breast cancer. Methods The miRNAs targetedly inhibiting RCOR3 expression were predicted using five software including RNA22,miRanda,Pic Tar,TargetScan and PITA,then the intersection of those miRNAs was performed. The effect of those miRNAs on negative regulation of RCOR3 expression was verified by high-throughput data,and the inhibitory effect of those miRNAs on RCOR3 expression was verified further by pan-cancer analysis. Results After intersection,miRNA-128-3 p,miRNA-27 a,miRNA-27 b and miRNA-19 b-3 p were obtained. MiRNA-128-3 p,miRNA-27 a,miRNA-27 b and miRNA-19 b-3 p negatively correlated with RCOR3 gene expression in breast cancer( all P < 0. 01). Pan-cancer analysis showed that miRNA-128-3 p was negatively correlated with RCOR3 gene expression in colorectal adenocarcinoma,lung adenocarcinoma,suprarenal epithelioma and endometrial carcinoma( all P < 0. 05),and miRNA-27 a was negatively correlated with RCOR3 expression in colorectal adenocarcinoma,bladder urothelial carcinoma,lung adenocarcinoma,lung squamous cell carcinoma,suprarenal epithelioma,endometrial carcinoma and acute myeloid leukemia( all P < 0. 05). Conclusion MiRNA-128-3 p,miRNA-27 a,miRNA-27 b and miRNA-19 b-3 p can potentially inhibit the expression of RCOR3 in breast cancer.
Objective To predict and validate by high-throughput data the micro RNA( miRNA) targetedly inhibiting REST corepressor 3( RCOR3) expression in breast cancer. Methods The miRNAs targetedly inhibiting RCOR3 expression were predicted using five software including RNA22,miRanda,Pic Tar,TargetScan and PITA,then the intersection of those miRNAs was performed. The effect of those miRNAs on negative regulation of RCOR3 expression was verified by high-throughput data,and the inhibitory effect of those miRNAs on RCOR3 expression was verified further by pan-cancer analysis. Results After intersection,miRNA-128-3 p,miRNA-27 a,miRNA-27 b and miRNA-19 b-3 p were obtained. MiRNA-128-3 p,miRNA-27 a,miRNA-27 b and miRNA-19 b-3 p negatively correlated with RCOR3 gene expression in breast cancer( all P < 0. 01). Pan-cancer analysis showed that miRNA-128-3 p was negatively correlated with RCOR3 gene expression in colorectal adenocarcinoma,lung adenocarcinoma,suprarenal epithelioma and endometrial carcinoma( all P < 0. 05),and miRNA-27 a was negatively correlated with RCOR3 expression in colorectal adenocarcinoma,bladder urothelial carcinoma,lung adenocarcinoma,lung squamous cell carcinoma,suprarenal epithelioma,endometrial carcinoma and acute myeloid leukemia( all P < 0. 05). Conclusion MiRNA-128-3 p,miRNA-27 a,miRNA-27 b and miRNA-19 b-3 p can potentially inhibit the expression of RCOR3 in breast cancer.
引文
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[14]Zhao N,Sun H,Sun B,et al. miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT:an essential role for Twist-1 in HCC[J].Sci Rep,2016,6:23091.
[15]Li L,Luo Z. Dysregulated miR-27a-3p promotes nasopharyngeal carcinoma cell proliferation and migration by targeting Mapk10[J]. Oncol Rep,2017,37(5):2 679-2 687.
[16]Salah Z,Arafeh R,Maximov V,et al. miR-27a and miR-27a*contribute to metastatic properties of osteosarcoma cells[J]. Oncotarget,2015,6(7):4 920-4 935.
[17]LüL,Mao X,Shi P,et al. MicroRNAs in the prognosis of triple-negative breast cancer:a systematic review and metaanalysis[J]. Medicine(Baltimore),2017,96(22):e7085.
[2]Boberg DR,Batistela MS,Pecharki M,et al. Copy number variation in ACHE/EPHB4(7q22)and in BCHE/MME(3q26)genes in sporadic breast cancer[J]. Chem Biol Interact,2013,203(1):344-347.
[3]Gokul G,Khosla S. DNA methylation and cancer[J]. Subcell Biochem,2013,61:597-625.
[4]Wang H,Liu S,Jia L,et al. Nanostructured lipid carriers for MicroRNA delivery in tumor gene therapy[J]. Cancer Cell Int,2018,18:101.
[5]Han Y,Li H. miRNAs as biomarkers and for the early detection of non-small cell lung cancer(NSCLC)[J]. J Thorac Dis,2018,10(5):3 119-3 131.
[6]Li JH,Liu S,Zhou H,et al. star Base v2. 0:decoding miRNAceRNA,miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data[J]. Nucleic Acids Res,2014,42(Database issue):D92-D97.
[7]Vasaikar SV,Straub P,Wang J,et al. Linked Omics:analyzing multi-omics data within and across 32 cancer types[J].Nucleic Acids Res,2017,46(D1):D956-D963
[8]Li M,Fu W,Wo L,et al. miR-128 and its target genes in tumorigenesis and metastasis[J]. Exp Cell Res,2013,319(20):3 059-3 064.
[9]Zhao L,Li R,Xu S,et al. Tumor suppressor miR-128-3p inhibits metastasis and epithelial-mesenchymal transition by targeting ZEB1 in esophageal squamous-cell cancer[J]. Acta Biochim Biophys Sin(Shanghai),2018,50(2):171-180.
[10]Lin Y,Wu Z. MicroRNA-128 inhibits proliferation and invasion of glioma cells by targeting COX-2[J]. Gene,2018,658(6):63-69.
[11]Liang RF,Li M,Yang Y,et al. Circulating miR-128 as a potential diagnostic biomarker for glioma[J]. Clin Neurol Neurosurg,2017,160:88-91.
[12]Jiang J,Feng X,Zhou W,et al. MiR-128 reverses the gefitinib resistance of the lung cancer stem cells by inhibiting the c-met/PI3K/AKT pathway[J]. Oncotarget,2016,7(45):73 188-73 199.
[13]Zhou L,Liang X,Zhang L,et al. MiR-27a-3p functions as an oncogene in gastric cancer by targeting BTG2[J]. Oncotarget,2016,7(32):51 943-51 954.
[14]Zhao N,Sun H,Sun B,et al. miR-27a-3p suppresses tumor metastasis and VM by down-regulating VE-cadherin expression and inhibiting EMT:an essential role for Twist-1 in HCC[J].Sci Rep,2016,6:23091.
[15]Li L,Luo Z. Dysregulated miR-27a-3p promotes nasopharyngeal carcinoma cell proliferation and migration by targeting Mapk10[J]. Oncol Rep,2017,37(5):2 679-2 687.
[16]Salah Z,Arafeh R,Maximov V,et al. miR-27a and miR-27a*contribute to metastatic properties of osteosarcoma cells[J]. Oncotarget,2015,6(7):4 920-4 935.
[17]LüL,Mao X,Shi P,et al. MicroRNAs in the prognosis of triple-negative breast cancer:a systematic review and metaanalysis[J]. Medicine(Baltimore),2017,96(22):e7085.
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