Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MiRNA expression profiling in human mammary epithelial cell (HMEC) CD24-CD44+ and non-CD24-CD44+ cell populations

ABSTRACT: To understand the role of p53 in regulating stem cell population (CD24-CD44+) and stemness-associated miRNAs, we first compared miRNA expression profiles between human mammary epithelical cells knocked-down p53 and control cells. We then cross-referenced p53-regulated miRNAs with stemness-associated miRNAs analyzed from expression profiling of sorted CD24-CD44+ and non-CD24-CD44+ cell populations. Further biological experiments were performed with the miRNAs that are altered in CD24-CD44+ stem cell populations and also regulated by p53. Total RNAs, including miRNAs, extracted from CD24-CD44+ cells (labeled in Hy3) and non-CD24-CD44+ cells (labeled in Hy5) were hybridized on Exiqon miRCURY LNA arrays according to the manufacturer's protocol.

ORGANISM(S): Homo sapiens

SUBMITTER: Mien C Hung

PROVIDER: E-GEOD-25036 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs.

Chang Chun-Ju CJ Chao Chi-Hong CH Xia Weiya W Yang Jer-Yen JY Xiong Yan Y Li Chia-Wei CW Yu Wen-Hsuan WH Rehman Sumaiyah K SK Hsu Jennifer L JL Lee Heng-Huan HH Liu Mo M Chen Chun-Te CT Yu Dihua D Hung Mien-Chie MC

Nature cell biology 20110220 3

The epithelial-mesenchymal transition (EMT) has recently been linked to stem cell phenotype. However, the molecular mechanism underlying EMT and regulation of stemness remains elusive. Here, using genomic approaches, we show that tumour suppressor p53 has a role in regulating both EMT and EMT-associated stem cell properties through transcriptional activation of the microRNA miR-200c. p53 transactivates miR-200c through direct binding to the miR-200c promoter. Loss of p53 in mammary epithelial ce ...[more]

PMID: 21336307

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Project description:Breast cancers contain a minority population of cancer cells characterized by CD44 expression but low or undetectable levels of CD24 (CD44+CD24-/low) that have higher tumorigenic capacity than other subtypes of cancer cells. METHODS: We compared the gene-expression profile of CD44+CD24-/low tumorigenic breast-cancer cells with that of normal breast epithelium. Differentially expressed genes were used to generate a 186-gene invasiveness gene signature (IGS), which was evaluated for its association with overall survival and metastasis-free survival in patients with breast cancer or other types of cancer. RESULTS: There was a significant association between the IGS and both overall and metastasis-free survival (P<0.001, for both) in patients with breast cancer, which was independent of established clinical and pathological variables. When combined with the prognostic criteria of the National Institutes of Health, the IGS was used to stratify patients with high-risk early breast cancer into prognostic categories (good or poor); among patients with a good prognosis, the 10-year rate of metastasis-free survival was 81%, and among those with a poor prognosis, it was 57%. The IGS was also associated with the prognosis in medulloblastoma (P=0.004), lung cancer (P=0.03), and prostate cancer (P=0.01). The prognostic power of the IGS was increased when combined with the wound-response (WR) signature. CONCLUSIONS: The IGS is strongly associated with metastasis-free survival and overall survival for four different types of tumors. This genetic signature of tumorigenic breast-cancer cells was even more strongly associated with clinical outcomes when combined with the WR signature in breast cancer. Expression profling was performed on 6 tumorigenic, 3 non tumorigenic samples of breast tumors and 3 normal breast samples on two different platforms GPL96 and GPL97. A gene signature was derived by comparing the gene expressions of 6 tumorigenic samples with 3 normal breast samples.

Dataset Information

MiRNA expression profiling in human mammary epithelial cell (HMEC) CD24-CD44+ and non-CD24-CD44+ cell populations

Publications

p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs.

Similar Datasets

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