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蚌埠医学院第一附属医院肿瘤外科
纸质出版日期:2020,
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[1]张卫建,张晖.HOTAIR与miRNA-148b-3p交互作用初步探究[J].西南医科大学学报,2020,43(02):140-145.
ZHANG Weijian, ZHANG Hui. Preliminary study of the interaction between HOTAIR and miRNA-148b-3p[J]. Journal of Southwest Medical University, 2020,43(2):140-145.
目的:通过生物信息学分析结合双荧光素酶实验探讨HOTAIR与hsa-miR-148b-3p是否存在结合
为下一步探究两者调控机制提供方向。方法:本研究于TCGA数据库中下载高通量表达miRNA数据
根据cut-off标准(P <0.05
log2FC> 2.0)
乳腺肿瘤与正常标本共检测到112个有差异性表达的miRNAs。从miRcode数据库中筛选HOTAIR靶标miRNA
其中包括miRNA-148b-3p在内55种miRNA。将上诉两组数据通过Veen diagram鉴别出重叠基因即miR-148b-3p、miR-204-5p、miR-375。用Kaplan-Meier曲线和对数秩和检验对上述三种miRNA进行生存分析。结果表明miR-148b-3p、miR-204-5p对乳腺癌患者生存有明显影响
而miR-375无明显差异。进而在starBase数据库中注意到其中只有miRNA-148b-3p与HOTAIR的超保守区域显示出> 10个碱基的互补性。最终双荧光素酶实验验证HOTAIR是否与hsa-miR-148b-3p结合。结果:通过Veen diagram对差异表达miRNAs和HOTAIR靶标miRNAs进行重叠数据筛选
然后进行生存分析
最终得出miR-148b-3p、miR-204-5p既在乳腺癌标本中有显著表达差异又对乳腺癌患者生存有明显影响
然而在starBase数据库中发现只有miRNA-148b-3p与HOTAIR结合。双荧光素酶实验表明HOTAIR与miR-148b-3p存在结合关系。结论:HOTAIR可能作为竞争性内源RNA(ceRNA)干扰miRNA-148b-3p对其靶基因的调控
从而影响乳腺癌的发生发展。
Objective: To explore whether HOTAIR is bound to hsa-miR-148 b-3 p through bioinformatic analy-sis and dual luciferase experiment
and to provide research directions for further exploration of the regulatory mecha-nism between the two. Methods: In this study
high-throughput miRNA data were downloaded from The Cancer Ge-nome Atlas database. According to the cut-off criteria(P < 0.05 and log2 FC > 2.0)
112 differentially expressedmiRNAs were identified between breast cancer specimens and normal specimens. The target miRNAs(55 miRNAsincluding miRNA-148 b-3 p) of HOTAIR were screened out from the miRcode database. The overlapping genes(i.e.
miR-148 b-3 p
miR-204-5 p
and miR-375) were identified from the above two sets of data using the Veen dia-gram. Then a survival analysis of the above three miRNAs was performed using the Kaplan-Meier curve andlog-rank sum test. The results showed that the survival of patients with breast cancer was significantly affected bymiR-148 b-3 p and miR-204-5 p
but not significantly affected by miR-375. In the starBase database
it was no-ticed that only miRNA-148 b-3 p showed complementarity of over 10 bases with the super-conserved regions of HO-TAIR. Finally
the dual luciferase experiment was used to validate whether HOTAIR was bound tohsa-miR-148 b-3 p. Results: Overlapping data were screened between differentially expressed miRNAs and the tar-get miRNAs of HOTAIR using the Veen diagram
and a survival analysis was performed. The results showed that significantly different expression was observed between miR-148 b-3 p and miR-204-5 p in breast cancer specimens
the two genes had significant effects on the survival of patients with breast cancer
but only miRNA-148 b-3 p wasbound to HOTAIR based on the data from the starBase database. The dual luciferase experiments showed the bind-ing between HOTAIR and miR-148 b-3 p. Conclusion: HOTAIR may interfere with the regulation of miR-NA-148 b-3 p on its target genes as a competitive endogenous RNA
thereby affecting the development and progres-sion of breast cancer. In this experiment
the potential association between miRNA-148 b-3 p and downstream ESR1 is also explored. The next step is to explore the role of the HOTAIR-miRNA-148 b-3 p-ESR1 pathway in the devel-opment and progression of breast cancer.
HOTAIRmiRNA-148b-3p乳腺癌Bioinformatics
HOTAIRmiRNA-148b-3pBreast cancerBioinformatics
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