Chen H, Qian K, Tang ZP, Xing B, Chen H, Liu N et al.. Bioinformatics and microarray analysis of microRNA expression profiles of murine embryonic stem cells, neural stem cells induced from ESCs and isolated from E8.5 mouse neural tube. Neurol Res 32: 603-613
Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Neurological Research
(Impact Factor: 1.44).
08/2009; 32(6):603-13. DOI: 10.1179/174313209X455691
To better understand whether microRNAs (miRNAs) are involved in the self-renewal of stem cells and fate determination of neural stem cells and to identify the miRNA expression patterns of different neural stem cells (NSC) in vitro and in vivo, we examined miRNA expression profiles of murine embryonic stem cells (ESC), NSC induced from ESC and isolated from E8.5 mouse neural tube (E8.5-NSC) using microarray technique. It was found that a total of 40 miRNAs had similar expression level in all the three cells [false discovery rate (FDR)=0, fold change <3.0]. Moreover, q-PCR showed that some members of miR-106b and miR-17-92 families were expressed in the ESC, NSC induced from ESC (ESC-NSC) and hematopoietic stem cells (HSC). Bioinformatical analysis showed that 'stemness genes' (p21/CDKN1A, p57/CDKN1C and PTEN) were putative targets of miR-106b and miR-17-92 families. A total of 95 miRNAs were found to experience significant change (FDR=0, fold change >5.0) when the ESC differentiated into NSC. On the basis of miRNA, mRNA expression variance and predicted target genes of miRNA, we formulated a bioinformatical model for miRNA control of ESC-NSC differentiation. Then, the miRNA expression pattern was compared between NSC obtained in vitro and in vivo, and it was found that only 8% of miRNAs were different between the two NSCs. This study suggested that miR-106b and miR-17-92 families may promote the renewal of stem cells by targeting PTEN, p21/CDKN1A and p57/CDKN1C. Some miRNAs may play a key role in gene re-programming during ESC-NSC differentiation, and a substantial homogeneity exists between NSCs derived in vitro and those in vivo.
Available from: PubMed Central
- "Our results provided evidences that miR-17 and miR-93, another member of miR-17 family can also repress BMPRII translation in primary neurons. This regulation is important since it is reported that miR-17 family is highly expressed in the early development of nervous system . The high level of miR-17 family may target BMPRII leading to the down-regulation of BMP signaling, while the repression of BMP signaling has been prove to facilitate neurogenesis . "
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ABSTRACT: Bone morphogenetic protein (BMP) signaling is active in many tissues including the central nervous system, in which it regulates cell proliferation, differentiation and maturation. The modulation of BMP pathway is crucial since abnormality of BMP signaling may cause cellular malfunction such as apoptosis. There are evidences indicating that miR-17 family is involved in the BMP signaling. In the present study, we demonstrated that BMP2 stimulation directly increased the transcription of miR-17-92 and miR-106b-25 cluster via Smad activation, which leads to the up-regulation of mature miR-17/20a/93. In addition, we provided evidence that BMP2 activation repressed BMPRII expression through modulating miR-17 family in primary neurons. Furthermore, we proved that such negative regulation protected neurons from apoptosis induced by abnormal BMP signaling. Taken together, these results suggest a regulatory pathway of BMP-miR-17 family-BMPRII, which consist a negative feedback loop that balances BMP signaling and maintains cell homeostasis in neurons.
Available from: jcs.biologists.org
- "The miRNA miR-17-92 cluster was first identified in the year 2005 as a potential human oncogene by He et al., and it was demonstrated that tumors derived from hematopoietic stem cells expressed a subset of the mir-17-92 cluster (He et al., 2005). miR-17-92 members have been identified as being overexpressed in numerous types of stem cells, such as hematopoietic stem cells (Jin et al., 2008), embryonal carcinoma SCs (Gallagher et al., 2009), mouse embryonic SCs (Gunaratne, 2009) and neuronal SCs (Chen et al., 2010), and are downregulated during neuronal lineage differentiation in unrestricted somatic stem cells (Iwaniuk et al., 2011) and in unrestricted somatic stem cells differentiated Fig. 7. Kaplan–Meier survival curves of gastric cancer patients expressing miR-20a or miR-92a. (A,B) Gastric cancer patients were ranked on the basis of the relative expression values obtained by real-time PCR and were divided into a high-expression group and low-expression group using the 50th percentile (median) as the cut-off point. "
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ABSTRACT: Human gastric cancers contain a population of gastric cancer stem cells (GCSCs) that can undergo self-renewal and multipotent differentiation. GCSCs can be enriched by EpCAM+/CD44+ gastric cancer cells. However, the mechanisms underlying how GCSCs balance self-renewal and differentiation remain to be explored. Because miRNAs can regulate cancer cell fates, we compared tumorspheric cancer cells enriched for GCSCs with more differentiated cells in terms of miRNA expression. We found that the miR-17-92 cluster members miR-19b, miR-20a and miR-92a were gradually reduced during the differentiation of GCSCs. Herein, we speculated that miR-17-92 members might function as regulators to sustain the self-renewal ability of GCSCs. By down-regulating miR-19b, miR-20a and miR-92a in EpCAM+/CD44+ GCSCs, or over-expressing them in EpCAM-/CD44- non-GCSC populations, we found that miR-19b, miR-20a and miR-92a could sustain the self-renewal function of GCSCs. Furthermore, we found that miR-19b, miR-20a and miR-92a could also promote the proliferation of gastric cancer cells. Moreover, miR-17-92 targeted the E2F1 and HIPK1 proteins, which suppressed Wnt-β-catenin signaling. A real-time PCR analysis of miR-19b, miR-20a and miR-92a expression in 97 gastric cancer specimens suggested that miR-92a could be used as an independent prognostic factor in gastric cancer. This study indicated that several members of the miR-17-92 cluster,miR-19b, miR-20a and miR-92a, might play significant roles in the development of gastric cancer stem cells and that miR-92a has the potential to be used as a predictive prognostic marker in gastric cancer.
Available from: spandidos-publications.com
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ABSTRACT: p57 is a cyclin-dependent kinase (CDK) inhibitor, the first cell cycle regulator that is regulated by imprinting. p57 was initially considered to be a tumor suppressor based on its ability to regulate cell cycle progression through its N-terminal domain. Now, it has been found that p57 is also involved in the regulation of other cellular processes including transcription, apoptosis, differentiation, development, and migration via its PAPA repeat and carboxyl-terminal domain. The multifunction of p57 participate in many processes in tumorigenesis involving in different mechanisms including loss of imprinting, loss of heterozygosity, promoter methylation, histone deacetylation and regulation of microRNAs. Moreover, upstream signaling pathways, protein-protein interactions and altered subcellular localization have also been reported to participate in abnormal expression of p57 resulting in the occurrence and progression of cancer. However, it is unclear whether p57 may play a dual role during tumorigenesis under different cellular processes similarly to its siblings. The presence of a nuclear localization signal in p57 is intriguing because it may affect the subcellular localization of p57, which can result in abnormal proliferation and motility of cells, and may be oncogenic under certain circumstances, as observed for p21 and p27.
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