| Summary: | 碩士 === 國立陽明大學 === 生物醫學資訊研究所 === 100 === Alternative polyadenylation (APA) could result in mRNA isoforms with variable length of 3’ UTRs. Gain of some microRNA target sites in 3’ UTR of a long mRNA isoform may cause different regulation from the corresponding short isoform. It has been known that cancer cells globally exhibit lower ratio of long and short isoforms (LSR), that is, they tend to express larger amount of short isoforms. To illustrate the relation between microRNA differential regulation and LSR, we analyzed published APA annotations, isoform expression and microRNA expression profiles of breast cancer and normal cells. Firstly, we found that the amount of microRNA target sites in alternative UTR (aUTR), the region only present in long isoforms, could affect LSR of the target genes. Secondly, we observed that the aUTR target genes of up-regulated microRNAs in tumor cells had overall lower LSR. Furthermore, the target sites of tumor-up-regulated microRNAs tended to appear in aUTR. Finally, we demonstrated that the amount of target sites of tumor-up-regulated microRNAs in aUTRs was correlated with the LSR change between cancer and normal cells. These results indicated that up-regulation of microRNAs might result in lower LSR of target genes in cancer cells through degradation of their long isoforms. This phenomenon can potentially contribute to the mechanism of global LSR decrease in cancer cells.
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