Concise Review: MicroRNA Expression in Multipotent Mesenchymal Stromal Cells

Lakshmipathy, Uma; Hart, Ronald P.

doi:10.1634/stemcells.2007-0625

Cited by 118 publications

(84 citation statements)

References 173 publications

(126 reference statements)

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“…Modulates the self-renewal of mesenchymal OGT, RBM24, CDK6 stem cells (28) miR-128 Up-regulated in the course of replicative senescence RLF, TRAF4, PHC1 of mesenchymal stem cells (37) miR-99a…”

Section: Resultsmentioning

confidence: 99%

A microRNA expression signature characterizing the properties of tumor-initiating cells for breast cancer

Wang

Zhang

et al. 2011

Oncology Letters

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Abstract. microRNAs (miRNAs) are involved in controlling tumor behaviors either as oncogenes or tumor suppressors. To elucidate the role of miRNAs in the regulation of tumor initiation, we delineated the microRNA expression signature characterizing the properties of tumor-initiating cells for breast cancer. A group of miRNAs were differentially expressed in MDA-MB-231 and SUM1315 cells (with a high proportion of breast cancer tumor-initiating cells, CD44 + CD24-/low subpopulation) compared to MCF-7 cells (only a small proportion of CD44 + CD24 -/low cells). Among the differentially expressed miRNAs common to MDA-MB-231 and SUM1315, approximately 46% of them are suggested to regulate the 'stemness' of stem cells or progenitor cells. Taken together, these findings suggested that miRNAs contribute to the maintenance of tumor-initiating properties and indicate the potential value of the miRNA expression signature in characterizing or predicting the features (including metastasis) of breast cancer. IntroductionThe leading cause of death in breast cancer (BrCa) patients is not the primary tumor in the breast per se, but metastasis to distant organs. Metastasis accounts for over 90% of deaths in BrCa patients. Millions of cells are released from the primary tumor into the blood circulation daily, but only a small minority of these cells survive and colonize on distant organs. The aim of the present study was to establish the identity of these cells. CD24-/low subpopulation in BrCa cells was reported to be enriched in BrCa T-ICs (2). This subpopulation of cells is capable of generating other cellular phenotypes observed in the original tumor and initiating metastases at distant sites from low numbers of cells (2). However, data on the characteristics of BrCa T-ICs and their molecular regulation is currently limited. microRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression by binding to their target miRNAs. miRNAs regulate tumor development, prognosis and metastasis either as oncogenes or tumor suppressors (3,4). A burgeoning body of evidence showed that miRNAs modulate the properties of embryonic stem (ES) and tissue stem cells in a variety of eukaryotic organisms (5,6). A group of miRNAs may play specialized roles in stem cell regulation, as the Dicer (the enzyme that processes the pre-miRNAs into mature miRNAs) knockout in mice is embryonically lethal (7), and Dicer conditional knockout mouse ES cells grow more slowly than controls and fail to differentiate (8).In the present study, we investigated the differences in miRNA expression profiling among BrCa cell lines with various proportions of T-ICs and the potential contribution of miRNAs to maintaining the 'stemness' of BrCa T-ICs. The results indicate that a miRNA expression signature may help identify the stemness of T-ICs, and that certain miRNAs may help predict clinical features, such as metastasis, for BrCa. Materials and methodsCell lines and cell culture. Human BrCa cell lines MCF-7, SUM149, SUM1315 and MDA-MB-231 were stored in...

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Section: Resultsmentioning

confidence: 99%

A microRNA expression signature characterizing the properties of tumor-initiating cells for breast cancer

Wang

Zhang

et al. 2011

Oncology Letters

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“…For example, macrophages and dentritic cells express miR-155 after TLR activation, which affects subsequent signaling by targeting TAB2 and SHIP1 (13)(14)(15). Several miRNAs, including miR-138, miR-335, miR-21, and miR-204 regulate differentiation of MSCs (16,(23)(24)(25). However, whether miRNAs play a role in the immunosuppression of MSCs is still unknown.…”

Section: Discussionmentioning

confidence: 99%

miR-155 Regulates Immune Modulatory Properties of Mesenchymal Stem Cells by Targeting TAK1-binding Protein 2

Ren

Cao

et al. 2013

Journal of Biological Chemistry

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Background:The molecular mechanisms underlining the immune regulatory property of mesenchymal stem cells (MSCs) are unknown. Results: Inflammatory cytokine-induced miR-155 reverses the immunosuppressive capacity of MSCs through inhibiting iNOS expression. Conclusion:The immune regulation-mediated by MSCs is tightly regulated by miR-155. Significance: This study revealed a novel role of miR-155 in regulating the immune modulatory activities of MSCs.

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“…Although many endogenous miRs have been identified in mammals, specific functions have remained largely undefined. However, recent studies indicate that the expression profiles of miRs in SCs are different from other tissues (27). This suggests that miRs may play an essential role in SC self-renewal, differentiation, and other functions (28).…”

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confidence: 99%

MicroRNA-146a Negatively Regulates the Immunoregulatory Activity of Bone Marrow Stem Cells by Targeting Prostaglandin E2 Synthase-2

Matysiak

Fortak-Michalska

Szymańska

et al. 2013

The Journal of Immunology

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The molecular mechanisms that regulate the immune function of bone marrow–derived mesenchymal stem cells (BMSCs) are not known. We have shown previously that freshly isolated BMSCs when induced to express neuronal stem cell markers lose immunoregulatory function when transferred into mice sensitized to develop experimental autoimmune encephalomyelitis. Recently, microRNAs (miRs) have been shown to be involved in the regulation of several immune responses in both innate and acquired immunity. We now show that among several differentially expressed miRs, miR-146a was strongly upregulated in neuronally differentiated when compared with miR-146a expression in freshly isolated BMSCs or control BMSCs cultured in parallel but in nondifferentiating medium. Inhibition of miR-146a with a selective antagomir restored the immunoregulatory activity of nBMSCs. We mapped miR-146a to its multiple predicted target mRNA transcripts and found that miR-146a was predicted to block PGE2 synthase (ptges-2). We then showed that Ptges-2 was directly targeted by miR-146a using a luciferase reporter assay. Furthermore, increased expression of miR-146a in BMSCs correlated with inhibition of PGE synthase-2 and inhibition of PGE2 release. Accordingly, inhibition of miR-146a restored synthesis of PGE2. These data support the conclusion that miR-146a plays a critical role in the control of the immunoregulatory potential of BMSCs.

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Concise Review: MicroRNA Expression in Multipotent Mesenchymal Stromal Cells

Cited by 118 publications

References 173 publications

A microRNA expression signature characterizing the properties of tumor-initiating cells for breast cancer

A microRNA expression signature characterizing the properties of tumor-initiating cells for breast cancer

miR-155 Regulates Immune Modulatory Properties of Mesenchymal Stem Cells by Targeting TAK1-binding Protein 2

MicroRNA-146a Negatively Regulates the Immunoregulatory Activity of Bone Marrow Stem Cells by Targeting Prostaglandin E2 Synthase-2

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