microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia

Han, Yoon-Chi; Park, Christopher Y.; Bhagat, Govind; Zhang, Jinping; Wang, Yulei; Fan, Jian‐Bing; Liu, Mofang; Zou, Yong-Rui; Gu, Hua

doi:10.1083/jcb1886oia12

Cited by 82 publications

(139 citation statements)

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“…As for lung cancer, growing evidence indicates that miR-29 family functions as tumor suppressor and most studies focus on the biology of miR29b [8,[20][21][22][23]. However, despite the high similarity of miR-29a/b/c mature sequence, studies have revealed that different isoforms of miR-29 family may exert distinct functions [24,25]. Concerning the tumor suppressive role of miR-29c in lung cancer, it has been demonstrated to revert aberrant methylation by targeting DNA methyltransferases 3A and 3B and inhibit metastasis by targeting integrin beta1 and matrix metalloproteinase 2 [20,22].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-29c Functions as a Tumor Suppressor by Targeting VEGFA in Lung Adenocarcinoma

Liu

Wu³

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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Section: Discussionmentioning

confidence: 99%

MicroRNA-29c Functions as a Tumor Suppressor by Targeting VEGFA in Lung Adenocarcinoma

Liu

Wu³

et al. 2017

International Journal of Radiation Oncology*Biology*Physics

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“…We found that two targets, Cdk6 and DNMT3A, are downregulated in miR-29 transgenic mice, whereas no differences in Mcl1 and Pten were detected (Fig. 6A) [although Pten is not a proven miR-29 target, it previously was predicted to be a potential target (14)]. …”

Section: Mir-29 Expression In Cll and Production Of The Eμ-mir-29 Tramentioning

confidence: 93%

“…On the other hand, one report showed that miR-29 expression is up-regulated in metastatic breast cancer, and a very recent study reported that miR-29 overexpression can cause acute myeloid leukemia (AML) in mice (13,14). To clarify the role of miR-29 in B-cell leukemias, we generated transgenic mice overexpressing miR-29 in B cells and now report the phenotype of this mouse model.…”

mentioning

confidence: 99%

Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression

Santanam

Zanesi

Efanov

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

151

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B-cell chronic lymphocytic leukemia (B-CLL), the most common leukemia in the Western world, occurs in two forms, aggressive (showing for the most part high ZAP-70 expression and unmutated IgH V H ) and indolent (showing low ZAP-70 expression and mutated IgH V H ). We found that miR-29a is up-regulated in indolent human B-CLL as compared with aggressive B-CLL and normal CD19 + B cells. To study the role of miR-29 in B-CLL, we generated Eμ-miR-29 transgenic mice overexpressing miR-29 in mouse B cells. Flow cytometric analysis revealed a markedly expanded CD5 + population in the spleen of these mice starting at 2 mo of age, with 85% (34/40) of miR-29 transgenic mice exhibiting expanded CD5 + B-cell populations, a characteristic of B-CLL. On average, 50% of B cells in these transgenic mice were CD5 positive. At 2 y of age the mice showed significantly enlarged spleens and an increase in the CD5 + B-cell population to ∼100%. Of 20 Eμ-miR-29 transgenic mice followed to 24-26 mo of age, 4 (20%) developed frank leukemia and died of the disease. These results suggest that dysregulation of miR-29 can contribute to the pathogenesis of indolent B-CLL.mouse models | microRNA C hronic lymphocytic leukemia (CLL) is the most common human leukemia, accounting for ∼30% of all cases (1), with ∼10,000 new cases observed each year in the United States. Characteristically, CLL is a disease of elderly people, with the incidence increasing linearly with each decade above age 40 y (1, 2). It is known that this disease is characterized by the clonal expansion of CD5 + B cells (2).MicroRNAs, representing between 1% and 3% of all eukaryotic genes, are a class of endogenous noncoding RNAs, 19-25 nt in size, which regulate gene expression at the transcriptional or translational level (3). Approximately half of human microRNAs are located at fragile sites and genomic regions involved in alterations in cancers (4), and alteration of microRNA expression profiles occurs in most cancers, suggesting that individual microRNAs could function as tumor suppressors or oncogenes (5).The 13q14 deletion is the most common CLL aberration and is detected by cytogenetic analysis in approximately half of the cases (6). Analysis of a deletion at 13q14.3 led to the discovery of two physically linked microRNAs, miR-15a and miR-16-1, as targets of these deletions (7). Consequently, miR-15a and miR-16-1 expression is reduced in the majority of CLL cases (7), and further studies indicated that miR-15a/miR-16-1 negatively regulate Bcl2 expression (8). These findings indicated that microRNAs play important roles in CLL and that down-regulation of miR-15/16 and subsequent Bcl2 up-regulation contribute to CLL pathogenesis (7). Because miR-15/16 was identified as a tumor suppressor in indolent CLL, the microRNA expression profile in CLL has been studied extensively, and a signature profile was reported describing 13 microRNAs that differentiate aggressive and indolent CLL (4).We and others observed that miRNA-29 expression is downregulated in aggressive CLL as compared ...

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“…3B, group 2). Notably, miR-29a was found to be up-regulated in highly enriched HSC populations ES 150 − and ES 150 + relative to SLAM populations or other progenitors (15). No miRNAs were expressed in all differentiated cells but not stem cells and progenitors.…”

Section: Comparison Of Mirna Expression Profiles In Different Cell Tymentioning

confidence: 95%

Comprehensive microRNA expression profiling of the hematopoietic hierarchy

Petriv

Kuchenbauer

Delaney

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

157

135

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The hematopoietic system produces a large number of highly specialized cell types that are derived through a hierarchical differentiation process from a common stem cell population. miRNAs are critical players in orchestrating this differentiation. Here, we report the development and application of a high-throughput microfluidic real-time quantitative PCR (RT-qPCR) approach for generating global miRNA profiles for 27 phenotypically distinct cell populations isolated from normal adult mouse hematopoietic tissues. A total of 80,000 RT-qPCR assays were used to map the landscape of miRNA expression across the hematopoietic hierarchy, including rare progenitor and stem cell populations. We show that miRNA profiles allow for the direct inference of cell lineage relations and functional similarity. Our analysis reveals a close relatedness of the miRNA expression patterns in multipotent progenitors and stem cells, followed by a major reprogramming upon restriction of differentiation potential to a single lineage. The analysis of miRNA expression in single hematopoietic cells further demonstrates that miRNA expression is very tightly regulated within highly purified populations, underscoring the potential of single-cell miRNA profiling for assessing compartment heterogeneity.RT-qPCR | stem cell | hematopoiesis | microfluidic | single cell

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microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia

Cited by 82 publications

References 1 publication

MicroRNA-29c Functions as a Tumor Suppressor by Targeting VEGFA in Lung Adenocarcinoma

MicroRNA-29c Functions as a Tumor Suppressor by Targeting VEGFA in Lung Adenocarcinoma

Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression

Comprehensive microRNA expression profiling of the hematopoietic hierarchy

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