miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression

Lee, Nan Sook; Kim, Jong Soo; Cho, Wha Ja; Lee, Man Ryul; Steiner, Riley; Gompers, Andrea; Ling, Daijun; Zhang, Jae; Strom, Pl; Behlke, Mark A.; Moon, Sung-Hwan; Salvaterra, Paul M.; Jove, Richard; Kim, Kye-Seong

doi:10.1016/j.bbrc.2008.09.159

Cited by 54 publications

(41 citation statements)

References 23 publications

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“…We have focused on the functional study of two closely related microRNAs, miR-10a and -10b, that showed the most prominent up-regulation upon RA treatment. Up-regulation of miR-10b was previously reported in RA-induced neuronal differentiation of human embryonal carcinoma NT2/D1 cells (76), and an increase in miR-10a could be detected during RA-induced differentiation of mouse embryonic stem cells into smooth muscle cells (68). This work reports that RA acts through NF-B binding to a consensus element in miR-10a gene promoter to induce miR10a expression.…”

Section: Discussionsupporting

confidence: 72%

MicroRNAs-10a and -10b Contribute to Retinoic Acid-induced Differentiation of Neuroblastoma Cells and Target the Alternative Splicing Regulatory Factor SFRS1 (SF2/ASF)

Meseguer

Mudduluru

Escamilla

et al. 2011

Journal of Biological Chemistry

106

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MicroRNAs (miRNAs) are an emerging class of non-coding endogenous RNAs involved in multiple cellular processes, including cell differentiation. Treatment with retinoic acid (RA) results in neural differentiation of neuroblastoma cells. We wanted to elucidate whether miRNAs contribute to the gene expression changes induced by RA in neuroblastoma cells and whether miRNA regulation is involved in the transduction of the RA signal. We show here that RA treatment of SH-SY5Y neuroblastoma cells results in profound changes in the expression pattern of miRNAs. Up to 42 different miRNA species significantly changed their expression (26 up-regulated and 16 down-regulated). Among them, the closely related miR-10a and -10b showed the most prominent expression changes. Induction of miR-10a and -10b by RA also could be detected in LA-N-1 neuroblastoma cells. Loss of function experiments demonstrated that miR-10a and -10b are essential mediators of RA-induced neuroblastoma differentiation and of the associated changes in migration, invasion, and in vivo metastasis. In addition, we found that the SR-family splicing factor SFRS1 (SF2/ASF) is a target for miR-10a -and -10b in HeLa and SH-SY5Y neuroblastoma cells. We show here that changes in miR10a and -10b expression levels may regulate SFRS1-dependent alternative splicing and translational functions. Taken together, our results give support to the idea that miRNA regulation plays a key role in RA-induced neuroblastoma cell differentiation. The discovery of SFRS1 as direct target of miR-10a and -10b supports the emerging functional interaction between two post-transcriptional mechanisms, microRNAs and splicing, in the neuronal differentiation context. MicroRNAs (miRNAs, miRs)5 are an emerging class of small non-coding endogenous RNAs that are involved in multiple biological processes. These tiny regulatory elements are transcribed as primary longer transcripts, which are then processed by Dicer and Drosha complexes into 21-23-nt mature miRNAs. One strand of the mature miRNA is then incorporated into the RNA-induced silencing complex to regulate gene expression by targeting the 3Ј-untranslated region (3Ј-UTR) of mRNAs with consequent translational repression and/or target mRNA degradation. This mode of action demonstrates the great regulatory potential of miRNAs, as a unique mRNA can be targeted by diverse miRNAs, and conversely, each miRNA may have 100s of different target mRNAs (for review, see Refs. 1 and 2).In vertebrates, the highest variety of miRNAs is expressed in the brain than in any other tissue, suggesting an important role in nervous system development (3, 4). Recent studies have revealed the importance of miRNA expression in neural development and differentiation. For instance, it has been reported that Dicer-deleted mice exhibit malformations of the midbrain and cerebellum and failure of neural crest and dopaminergic differentiation (5). In addition, three brain-specific miRNAs (miR-124a, miR-9, and miR-132) have been proposed to regulate the transcription factor R...

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Section: Discussionsupporting

confidence: 72%

MicroRNAs-10a and -10b Contribute to Retinoic Acid-induced Differentiation of Neuroblastoma Cells and Target the Alternative Splicing Regulatory Factor SFRS1 (SF2/ASF)

Meseguer

Mudduluru

Escamilla

et al. 2011

Journal of Biological Chemistry

106

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“…Members of the mir-302 family are down-regulated rapidly in response to embryonic stem cell (ESc) differentiation (32). Lee et al also demonstrated that functional miR-302b is necessary to maintain stem cell self-renewal and inhibit the differentiation of human embryonic carcinoma cells (Eccs) (33), which is consistent with our results. The function of these miRNAs, and the mechanism by which they participate in heart development, requires further study.…”

Section: Discussionsupporting

confidence: 91%

Differential expression of microRNAs in cardiac myocytes compared to undifferentiated P19 cells

Liu²,

Chen³

et al. 2011

Int J Mol Med

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Abstract. microRNA (miRNA) expression is tightly controlled in a tissue-specific and developmental stage-specific manner; some are highly and specifically expressed in cardiovascular tissues. miRNA expression profiling, using miRNA microarrays facilitates studying the biological function of miRNAs. We investigated changes in miRNA expression profiles during differentiation of P19 cells into cardiac myocytes in order to elucidate the mechanisms of heart development. The morphology of P19 cells during differentiation was observed using an inverted microscope. Western blot analysis was performed to detect cardiac troponin I (cTnI) expression. Total RNA was extracted from P19 cells for microarray and real-time quantitative reverse transcription-polymerase chain reaction (real-time qRT-PcR) analyses to determine the miRNA expression profile. The miRNA microarray revealed differential expression of 49 miRNAs, of which 26 were down-regulated and 23 were up-regulated in differentiated cardiac myocytes, compared to normal P19 cells. This was confirmed by realtime qRT-PcR. We also utilized target prediction analysis to identify gene targets. Some miRNAs may have important roles in cardiac development and congenital heart defects (CHDs). Further analysis of miRNA function to confirm their target genes during cardiac development will determine the potential for novel miRNA-based therapeutic strategies.

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“…46 miR-302 directly targets at least two components of the cell cycle machinery, Cyclins D1 and D2, which are expressed at low levels in hESCs. 46,57 How the inhibition of these D-type Cyclins accelerates the cell cycle and whether other cell cycle regulators are targeted by miR-302 in hESCs remain open questions. Recently, another hESC-enriched miRNA, miR-92b, has been implicated in the regulation of cell cycle.…”

Section: Embryonic Stem Cellsmentioning

confidence: 99%

MicroRNAs in early vertebrate development

Rosa

Brivanlou

2009

Cell Cycle

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miR-302b maintains “stemness” of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression

Cited by 54 publications

References 23 publications

MicroRNAs-10a and -10b Contribute to Retinoic Acid-induced Differentiation of Neuroblastoma Cells and Target the Alternative Splicing Regulatory Factor SFRS1 (SF2/ASF)

MicroRNAs-10a and -10b Contribute to Retinoic Acid-induced Differentiation of Neuroblastoma Cells and Target the Alternative Splicing Regulatory Factor SFRS1 (SF2/ASF)

Differential expression of microRNAs in cardiac myocytes compared to undifferentiated P19 cells

MicroRNAs in early vertebrate development

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