CAJ | 학술논문

目的：探索 miRNA-148a 在膀胱癌发生发展中的作用。方法收集35例膀胱癌组织和16例非癌组织，采用荧光定量 PCR 方法检测 miRNA-148a 的相对表达量，并分析其与临床特征的相关性；采用生物信息学分析，预测 miRNA-148a的靶基因和转录因子，构建 TF-miRNA-148a-靶基因调控网络图，并对其靶基因进行 GO 富集和 KEGG Pathway 分析。结果miRNA-148a 在膀胱癌中的相对表达量（0.0008±0.0002）明显低于非癌组织（0.0021±0.0005）（t＝2.46，P ＜0.05），其相对表达量在不同性别、年龄、病理分级、临床分期、淋巴结转移组的差异无统计学意义（P ＞0.05）。3个软件都预测到的 miRNA-148a 靶基因268个；预测到 miRNA-148a 的转录因子60个，结合评分＞80的结合位点657个；对268个靶基因进行 GO 富集分析，发现其靶基因主要涉及神经细胞分化、发育、增殖、mRNA 合成，蛋白连接等众多的生物学过程（P ＜0.001，相对于背景具有统计意义）；KEGG Pathway 分析发现268个靶基因参与 p53，恶性肿瘤、前列腺癌、PI3K-AKT 等信号通路（P ＜0.05，相对于背景具有统计意义）；根据构建的 TF-miRNA-148a-靶基因调控网络图，挖掘出可能调控 miRNA-148a 的转录因子有 SP1，ESR1，AP1，MYC，BRCA1等；可能受 miRNA-148a 调控的基因有 IGF1，P27 kip1，NCOA1，PTEN， SERPINE1等。结论miRNA-148a 在膀胱癌中表达下调，可能参与膀胱癌的发生发展，生物信息学分析为后续研究提供一定的思路。
목적：탐색 miRNA-148a 재방광암발생발전중적작용。방법수집35례방광암조직화16례비암조직，채용형광정량 PCR 방법검측 miRNA-148a 적상대표체량，병분석기여림상특정적상관성；채용생물신식학분석，예측 miRNA-148a적파기인화전록인자，구건 TF-miRNA-148a-파기인조공망락도，병대기파기인진행 GO 부집화 KEGG Pathway 분석。결과miRNA-148a 재방광암중적상대표체량（0.0008±0.0002）명현저우비암조직（0.0021±0.0005）（t＝2.46，P ＜0.05），기상대표체량재불동성별、년령、병리분급、림상분기、림파결전이조적차이무통계학의의（P ＞0.05）。3개연건도예측도적 miRNA-148a 파기인268개；예측도 miRNA-148a 적전록인자60개，결합평분＞80적결합위점657개；대268개파기인진행 GO 부집분석，발현기파기인주요섭급신경세포분화、발육、증식、mRNA 합성，단백련접등음다적생물학과정（P ＜0.001，상대우배경구유통계의의）；KEGG Pathway 분석발현268개파기인삼여 p53，악성종류、전렬선암、PI3K-AKT 등신호통로（P ＜0.05，상대우배경구유통계의의）；근거구건적 TF-miRNA-148a-파기인조공망락도，알굴출가능조공 miRNA-148a 적전록인자유 SP1，ESR1，AP1，MYC，BRCA1등；가능수 miRNA-148a 조공적기인유 IGF1，P27 kip1，NCOA1，PTEN， SERPINE1등。결론miRNA-148a 재방광암중표체하조，가능삼여방광암적발생발전，생물신식학분석위후속연구제공일정적사로。
Objective To explore the role of miRNA-148a in bladder tumorous development and progression.Methods Ex-pression of miRNA-148a was assessed in 35 bladder carcinoma tissues and 16 non-carcinoma tissues by fluorescence quanti-tative real time PCR,and correlation with clinical features was evaluated.Target genes and transcription factors of miRNA-148a were predicted using bioinformatic analysis,then TF-miRNA-148a-target genes network diagram was built and the tar-get genes was analyzed of gene ontology enrichment and KEGG pathway.Results Expression of miRNA-148a was lower in bladder carcinoma tissues than in non-carcinoma tissues(0.000 8±0.000 2 vs 0.002 1±0.000 5)(t=2.46,P <0.05),but its expression was no statistical significance in different groups of gender,age,pathological classification,clinical stage, lymph node metastasis (P >0.05).268 target genes of miRNA-148a were predicted by three softwares at the same time,60 transcription factors were predicted and the binding sites with combination scroes above 80 was 657.The target genes of miRNA-148a was enriched in many biological processes,such as neuron differentiation,generation of neurons,neuron projec-tion development,cytoplasmic mRNA processing body,cytoplasm(P <0.001).They also participated in p53 signaling path-way,proteoglycans in cancer-homo sapiens,pathways in cancer,prostate cancer,protein processing in endoplasmic reticulum, focal adhesion and so on(P <0.05).According to TF-miRNA-148a-target genes network diagram,miRNA-148a was regula-ted by SP1,ESR1,AP1,MYC and BRCA1,genes of IGF1,P27kip1 ,NCOA1,PTEN,SERPINE1 might be regulated by miR-NA-148a.Conclusion miRNA-148a which was significantly down-regulation in bladder carcinoma tissues may be participate in bladder tumorous development and progression,bioinformatics analysis provides some ideas for further research.