Gene Regulatory Networks of Artificial MicroRNA p-27-5p-Treated Human Breast Cancer Cell Line T-47D
Date Issued
2010
Date
2010
Author(s)
Hsu, Chung-Cheng
Abstract
MicroRNAs (miRNAs) are small, endogenous non-coding RNAs of 20–23 nucleotides in length that negatively regulate the expression of target genes at the post-transcriptional level. miRNAs have recently emerged as important regulators that play significant roles in tumorigenesis. The present study attempted to elucidate the functions of p-27-5p, a novel possible miRNA we recently discovered (Chang et al. 2008). In our study, we found that cell growth exhibited a decrease and showed that the breast cancer cell line T-47D were induced to arrest at G0/G1 phase after treatment with p-27-5p mimic. To understand the regulatory mechanism of p-27-5p, we performed exon array and Ingenuity Pathway Analysis to construct gene expression networks of p-27-5p-treated breast cancer cell line T-47D. The results demonstrated that several genes associated with cancer cell apoptosis or proliferation experienced an expression change after p-27-5p treatment. We demonstrated that cyclin-dependent kinase 4 (CDK4) is the target of p-27-5p by using luciferase reporter assay. Previous studies indicated that CDK4 can stimulate cell cycle progression and is often overexpressed in cancer cells. We also demonstrated that p-27-5p downregulates CDK4 protein expression and RB1 phosphorylation by using western blotting. Taken together, our data suggest this artificial miRNA, p-27-5p, plays an important role in cancer progression and has the potential to be applied in breast cancer therapy.
Subjects
miRNAs
breast cancer
cell cycle
exon array
regulatory network
SDGs
Type
thesis
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