Cancer remains the No.1 killer in Taiwan, according to the report from Department of Health, Executive Yuan, R.O.C. (Taiwan), 40,305 people were killed in 2007 (Data source: http://www.doh.gov.tw/CHT2006/index_populace.aspx). On average, cancer claims a life in Taiwan about every 13 minutes.
There are five major steps for cancer development: initiation, promotion, malignant conversion, progression, and metastasis. The formation of cancer is the combined interaction of tumor suppressor genes and cancer inducer genes (oncogenes).
Although several genes, including oncogenes and tumor suppressor genes, have been identified in human genomes, most of the mechanism of cancer formation is still unknown. Recent studies indicate miRNAs may provide new insight in cancer research.
Using up- or downregulated expression of the cancer-related miRNAs is a good approach to study the function of miRNAs in cancer pathogenesis.
We developed a systematic analysis method by to identify the roles of miRNAs in cancers. 205 cancer-related miRNAs were collected in the first step, and then their transcription start sites (TSS) were identified by experimental and computational data.
We analyzed cis-regulatory elements from promoter regions as 3-kb segment upstreams of TSS by using Match program with TRANSFAC database. All the putative transcription factors were involved in syn-regulated expression patterns of miRNA and coding genes among 15 tissues. After understanding the potential elements result up or downregulation of miRNAs, we analyzed the cancer-related miRNA functions. The cancer-related miRNA targets were predicted by miRanda program and the expression of miRNA targets were checked by tumor microarray data. We selected the tissue-specific miRNAs which were most differentially expressed in certain tissues. All
Chapter 7 Conclusion
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the cis-regulatory elements and miRNA target genes were annotated the molecular function by Gene Ontology database. Finally the miRNA regulatory networks were identified in 8 cancers. Understanding of the function of miRNAs can provide the new insights on the mechanism of tumorgenesis, and new biomarkers for cancer.
94
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