Bioinformatics-based Analysis for microRNAs Expression Profiles between Basal-like and Luminal A Breast Cancers
-
摘要: 目的 对基底型和Luminal A型乳腺癌microRNAs表达谱进行分析，找出两种分子亚型乳腺癌之间差异表达的microRNAs，并对差异表达microRNAs在不同分子亚型乳腺癌中可能发挥的生物学功能进行初步探讨。 方法 从公共基因芯片数据库GEO中筛选基底样型和Luminal A型乳腺癌microRNAs表达谱数据，利用BRB-arrayTools软件筛选出差异表达的microRNAs。对差异表达的microRNAs，利用TargetScan和miRDB靶基因预测软件及TarBase数据库获得可能的靶基因集。利用DAVID数据库，对差异表达micorRNAs的靶基因集进行进一步Gene Ontology和信号通路分析。 结果 通过对基底样型和Luminal A型乳腺癌microRNAs表达谱分析获得54个差异表达的microRNAs（P≤0.001）。相对于Luminal A亚型乳腺癌，31个microRNAs在基底样型乳腺癌中上调表达，而23个microRNAs下调表达。上调和下调表达microRNAs可能的靶基因集数目分别为4 916和3 217个。对于上调和下调microRNAs的靶基因集，Gene Ontology分析表明，两个靶基因集分别在不同的生物学过程显著富集；KEGG通路分析分别涉及了35条和39条（P≤0.05）；BIOCARTA通路分析则分别涉及5条和9条（P≤0.05）。 结论 本研究获得了基底样型和Luminal A型乳腺癌差异表达的microRNAs，并通过靶基因功能分析获得差异表达microRNAs在两种分子亚型乳腺癌之间可能参与的不同生物学过程及信号通路，可能在不同分子亚型乳腺癌中发挥不同的调节作用。
-
关键词:
- 乳腺癌 /
- 基底样型 /
- Luminal A型 /
- 微小RNAs /
- 生物信息学
Abstract: Objective To explore differently expressed microRNAs between basal and Luminal A subtype of breast cancers and study the regulatory roles of these microRNAs. Methods A dataset of microRNAs expression profilings of basal and Luminal A subtype of breast cancers was obtained from GEO database and analyzed by BRB-ArrayTolls. Target gene sets were collected by prediction software TargetScan, miRDB and TarBase. And then Gene Ontology categories and pathways of target gene sets were further analyzed by DAVID database. Results Up-regulation of 31 microRNAs and down-regulation of 23 microRNAs were identified in basal compared with Luminal A breast cancers (P≤0.001). Correspondingly, two gene sets of 4 916 and 3 217 target genes were collected. Further Gene Ontology analyses showed that different Gene Ontology categories were enriched between two target gene sets. There were 35 and 39 KEGG pathways (P≤0.05) were enriched separately in two target gene sets. Also, 5 and 9 BIOCARTA pathways were enriched (P≤0.05). Conclusion There are different microRNAs expression patterns between Basal and Luminal A breast cancers.Function analysis indicated that differently expressed microRNAs may take partin quite different biological processes and signaling pathways, and may have different regulating roles in different breast cancers.-
Key words:
- Breast cancer /
- Basal /
- Luminal A /
- microRNAs /
- Bioinformatics
-
-
[1] Pasquinelli AE. MicroRNAs and their targets: recognition, regulation and an emerging reciprocal relationship[J]. Nat Rev Genet, 2012, 13(4): 271-82. [2] Lujambio A, Lowe SW. The microcosmos of cancer[J].Nature,2012,482(7385):347-55. [3] Sotiriou C, Pusztai L. Gene-expression signatures in breast cancer[J]. N Engl J Med,2009,360(8):790-800. [4] van 't Veer LJ, Dai H, van de Vijver MJ, et al. Gene expression profiling predicts clinical outcome of breast cancer[J]. Nature，2002,415(6871):530-6. [5] Foulkes WD,Smith IE,Reis-Filho JS.Triple-negative breast cancer[J].N Engl J Med,2010,363 (20):1938-48. [6] Lowery AJ, Miller N, Devaney A, et al.MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer[J]. Breast Cancer Res,2009,11 (3):R27. [7] Zhu M, Yi M, Kim CH,et al.Integrated miRNA and mRNA expression profiling of mouse mammary tumor models identifies miRNA signatures associated with mammary tumor lineage[J].Genome Biol,2011,12(8):R77. [8] Huang L, Ting D, Lin X, et al. MicroRNA-224 targets RKIP to control cell invasion and expression of metastasis genes in human breast cancer cells[J].Biochem Biophys Res Commun,2012,425 (2):127-33. [9] Zhu S, Sachdeva M, Wu F, et al. Ubc9 promotes breast cell invasion and metastasis in a sumoylation-independent manner[J].Oncogene,2010,29(12):1763-72. [10] Zhou X, Marian C, Makambi KH, et al. MicroRNA-9 as potential biomarker for breast cancer local recurrence and tumor estrogen receptor status[J].PLoS One,2012,7(6):e39011. [11] Zhu L, Chen H, Zhou D, et al. MicroRNA-9 up-regulation is involved in colorectal cancer metastasis via promoting cell motility[J].Med Oncol,2012,29(2):1037-43. [12] de Souza Rocha Simonini P, Breiling A, Gupta N, et al. Epigenetically deregulated microRNA-375 is involved in a positive feedback loop with estrogen receptor alpha in breast cancer cells[J].Cancer Res,2010,70(22):9175-84. [13] Ward A, Balwierz A, Zhang JD, et al.Re-expression of microRNA-375 reverses both tamoxifen resistance and accompanying EMT-like properties in breast cancer[J].Oncogene,2013，32（9） ：1173-82. [14] Bartel DP. MicroRNAs: target recognition and regulatory functions[J]. Cell,2009,136(2): 215-33.
计量
- 文章访问数: 2167
- HTML全文浏览量: 21
- PDF下载量: 318
下载:
