Screening Of Breast Cancer Related MicroRNA By Bioinformatics

Objective: Bioinformatics analysis methods and analysis tools were used to further analyze the differentially expressed mi RNA from breast cancer and para-cancer tissues,and the differentially expressed mi RNA from functional studies,molecular pathways and protein interaction net works,to find the mi RNA related to breast cancer。Methods: 1.Download mi RNA expression in breast cancer and adjacent tissues from TCGA database;2.Used R language and package to process download data,and diff erentially expressed mi RNA in breast cancer;3.Functional analysis of differentially expressed mi RNA;4.Target gene prediction was carried out for mirnas significantly dif ferentially expressed;5.The online analysis tools Aimgo2,DAVID and STRING were use d to analyze the GO,KEGG and protein-protein interaction networks of the obtained target genes.Results: 1.By analysis of 1,881 mi RNA expressions in 1096 breast cancer ti ssues and 104 paracancer tissues downloaded from TCGA data showed that 158 mi RNA expressions were up-regulated and 97 mi RNA expres-si ons were down-regulated.The expression of mi RNA-21 was significantly up-regulated(Log FC = 6.506886397,P <0.05).The expre-ssion of mir-328 was significantly down-regulated(Log FC =-6.559142257 P <0.05).2.Down-regulated mi RNA mainly involves GO function as mi RNA silencing of genes,and KEGG enrichment function is related to tumor mi RNA.Up-regulation of mi RNA mainly involves the GO function: miRNA silencing of genes,regulation of neovascularization,mi RNA-mediat ed translation inhibition,negative regulation of muscle cell apoptosis,re gulation of lipoprotein particle clearance,negative regulation of resistanc e response and regulation of endothelial cell apoptosis.KEGG enrichment was mainly involved in tumor-related mi RNA.3.The target genes of hsa-mi R-21-5p were obtained by online analysis databases "Target Scan","mi RWalk" and "mi RDB" respectively,and a total of 78 target genes including ZNF367 and IL12 A were obtained from the intersection of the three data sets.4.The enrichment functions of GO and KEGG of mir-21 target gen es were verified.It was found that the GO function of the target gene w as mainly enriched in the following aspects: biological function: anatomi cal structure,morphological generation and regulation,developmental pro cess regulation,and cell differentiation.The molecular functions: DNA bi nding transcriptional activation,specific binding of RNA polymerase II,regulation of development process,and specific binding of RNA polyme rase II to DNA regulatory region.In terms of cell component function,it is mainly involved in the composition of chromatin and membrane org anelles.The KEGG enrichment function analysis using the online tool "D AVID 6.8" showed that its function mainly concentrated in the tumor-re lated pathways and cell cycles,among which,it was related to the tum or-developing pathways of prostate cancer and colon cancer.The "STRIN G" protein-protein network analysis revealed that the major genes involv ed were PIK3R1(phosphatidylinositol 3 kinase regulation subunit 1)、 S TAT3(signal transduction and transcription factor 3),and so on.5.GO analysis of mir-328 target genes revealed that the gene GO functions were mainly concentrated in biological functions: regulation of synaptic plasticity,regulation of developmental process,signaling pathw ay of transmembrane receptor protein tyrosine kinase,cell differentiation,and regulation of trans-synaptic signals.The molecular functions are as follows: protein kinase binding,proximal promoter sequence specific DNA binding,transcriptional regulation region sequence specific DNA bindi ng,etc.In terms of the function of cell components,it is mainly involve d in cationic channel complex and double-stranded DNA binding.KEGG enrichment was mainly concentrated in 19 pathways and played a role in the signaling pathway of c AMP,MAPK,cancer-related proteoglycan and endometrial cancer.The protein-protein interaction network suggeste d that mir-328 target genes are related to the activation of ras-like GTP ases(gtpase-activator protein for ras-like GTPases),and that DAB2 IP,I QGAP3,RASA4,and SYNGAP1 play a major role in their regulation.Conclusions: 1.There were differences in mi RNA expression between breast can cer and paracancer tissues.2.Mir-21,h SA-Mir-141,h SA-Mir-126 and other mirnas were up-re gulated in breast cancer tissues compared with paracancer tissues,while the expressions of h SA-Mir-328,HSA-let-7D,h SA-Mir-197 and other mi rnas were down-regulated in breast cancer tissues compared with paraca ncer tissues.3.Target genes of Mir-21 are closely related to cell cycle and tum or signaling pathway,among which the key target genes include PIK3R1 and STAT3.Mir-21 is closely related to the growth,metastasis and dr ug resistance of various tumors including breast cancer,and may be a p otential prediction and therapeutic target for breast cancer.4.Mir-328 is associated with a variety of transmembrane and transsynaptic signaling pathways including PI3K/AKT,c AMP and MAPK.