Insertion of microRNA-125b-1, a human homologue of lin-4, into a rearranged immunoglobulin heavy chain gene locus in a patient with precursor B-cell acute lymphoblastic leukemia

Sawada, Takashi; Iwanaga, Eisaku; Mitsuya, Hiroaki; Asou, Norio

doi:10.1038/sj.leu.2403938

Cited by 109 publications

(88 citation statements)

References 8 publications

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“…7 RT-PCR using primers set at VH and Cm produced two PCR products (390 and B170 bp). (c) Relative expression levels of miR125b were examined by real-time PCR in 293T cells transduced with pMXsEF1-IGH/miR-125b-1-(GFP), miR-125b expression vector (pMXsEF1-miR-125b-(GFP)) or mock (pMXsEF1-(GFP)).…”

Section: Mir125bmentioning

confidence: 99%

“…A miRNA expression cassette was constructed in the opposite direction from a GFP expression cassette. Expression fragments of miR-125b or IGH/ miR-125b-1 were PCR amplified from C57BL/6 mouse genomic DNA or cDNA of tumor derived from a BCP-ALL patient, 7 respectively. Primer pairs are described in 'Supplementary Materials and methods'.…”

Section: Vector Constructionmentioning

confidence: 99%

“…5,6 An evolutionally conserved miRNA, miR-125b, has been implicated in human cancers. [7][8][9][10][11][12] MiR-125b-1, mapped on 11q24, has been found to be a target of recurrent chromosomal abnormalities seen in both lymphoid and myeloid malignancies. [7][8][9][10] We previously reported an insertion of miR-125b-1 into the IGH locus in a patient with B-cell precursor acute lymphoblastic leukemia (BCP-ALL).…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10] We previously reported an insertion of miR-125b-1 into the IGH locus in a patient with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). 7 Subsequently, other groups identified fusion sequences of IGH and miR-125b-1 from t(11;14)(q24;q32). 9,10 Bousquet et al 8 identified miR-125b-1 as a gene involved in t(2;11)(p21;q23) observed in patients with myelodysplastic syndrome and acute myeloid leukemia (AML).…”

Section: Introductionmentioning

confidence: 99%

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Eμ/miR-125b transgenic mice develop lethal B-cell malignancies

et al. 2011

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MicroRNA-125b-1 (miR-125b-1) is a target of a chromosomal translocation t(11;14)(q24;q32) recurrently found in human B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This translocation results in overexpression of miR-125b controlled by immunoglobulin heavy chain gene (IGH) regulatory elements. In addition, we found that six out of twenty-one BCP-ALL patients without t(11;14)(q24;q32) showed overexpression of miR-125b. Interestingly, four out of nine patients with BCR/ABL-positive BCP-ALL and one patient with B-cell lymphoid crisis that had progressed from chronic myelogenous leukemia overexpressed miR-125b. To examine the role of the deregulated expression of miR-125b in the development of B-cell tumor in vivo, we generated transgenic mice mimicking the t(11;14)(q24;q32) (El/miR-125b-TG mice). El/miR-125b-TG mice overexpressed miR-125b driven by IGH enhancer and promoter and developed IgM-negative or IgM-positive lethal B-cell malignancies with clonal proliferation. B cells obtained from the El/miR-125b-TG mice were resistant to apoptosis induced by serum starvation. We identified Trp53inp1, a proapoptotic gene induced by cell stress, as a novel target gene of miR-125b in hematopoietic cells in vitro and in vivo. Our results provide direct evidence that miR-125b has important roles in the tumorigenesis of precursor B cells.

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Section: Mir125bmentioning

confidence: 99%

Section: Vector Constructionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eμ/miR-125b transgenic mice develop lethal B-cell malignancies

et al. 2011

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“…miRNAs can function as tumor suppressors or oncogenes, depending on their specific target genes (6,7). For example, miR-145, miR-335, miR-125b-1, miR-126, miR-15a, miR-16-1, miR-31, and miR-335 are all tumor suppressors for specific cancer types (8)(9)(10)(11). Recent studies have shown that miRNAs are involved in the malignant progression of breast cancer (12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Sun

et al. 2016

Oncology Reports

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Abstract. MicroRNA (miRNA) is a type of endogenous non-coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines. To study the functional significance of miR-124, we overexpressed miR-124 with miR-124 mimics and observed breast cancer cell proliferation, colony formation, migration, and invasion abilities by in vitro cell culture experiments. Target prediction algorithms and luciferase reporter gene assays were used to identify the target genes of miR-124. We also knocked down miR-124 targets using short hairpin RNA (shRNA) constructs, and observed associated breast cancer cell characteristics by in vitro cell culture experiments. We found that miR-124 expression significantly decreased in breast cancer tissues and cells compared to normal tissues and cells. In addition, cell proliferation, colony formation, migration, and invasion were decreased after overexpression of miR-124 in breast cancer cells. Furthermore, we used several algorithms to identify the snail family zinc finger 2 (SNAI2) as a potential target gene of miR-124. The protein expression level and luciferase activity of the 3'-untranslated region of SNAI2 were significantly decreased in breast cancer cells transfected with miR-124 mimics. Cell proliferation, colony formation, migration, and invasion were also decreased after knockdown of SNAI2 by shRNA. In conclusion, our data suggest that miR-124 expression is decreased in breast cancer and plays an important role as a tumor suppressor gene by targeting SNAI2. These findings may reveal novel perspectives for clinical treatments against breast cancer.

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MicroRNA Signatures as Biomarkers in Cancer

Adams

Slack

2015

Encyclopedia of Life Sciences

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Microribonucleic acids (miRNAs) are a class of small noncoding RNAs that regulate gene expression posttranscriptionally and control many biological processes including tumourigenesis. Given that, miRNA levels are heavily dysregulated in tumour tissues, many of these RNAs have been identified as classifiers for particular cancer subtypes. In addition, miRNA gene signatures can provide prognostic value, are associated with tumourigenic processes such as metastasis and can identify certain tumour cell types including drug‐resistant and cancer stem cell populations. To gain a better molecular understanding of therapeutic response and disease relapse, there has been an impetus to develop miRNA biomarker profiles through less invasive strategies (i.e. from serum and other sources) rather than from repeated biopsy near the original tumour site. Through these techniques, miRNAs have been found to exist in cell‐free fractions, in exosomes and in circulating tumour cells. While it is still unclear about the mechanisms guiding the release of miRNAs into the serum and other sources, overall, miRNAs have the potential to be used in understanding the pathogenesis of disease prognosis and for diagnostic purposes and in the development of new therapeutic treatment regimens. Key Concepts MicroRNAs function as master regulators of gene expression at the posttranscriptional level. MicroRNAs can function as oncogenes or tumour suppressors in a cell‐context‐dependent manner. MicroRNAs are stable, found in serum and other biofluids and make good non‐invasive biomarkers. MicroRNA profiles are associated with therapeutic treatments and disease outcomes. MicroRNAs can themselves be therapeutic agents or therapeutic targets.

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Insertion of microRNA-125b-1, a human homologue of lin-4, into a rearranged immunoglobulin heavy chain gene locus in a patient with precursor B-cell acute lymphoblastic leukemia

Abstract: Insertion of microRNA-125b-1, a human homologue of lin-4, into a rearranged immunoglobulin heavy chain gene locus in a patient with precursor B-cell acute lymphoblastic leukemia Leukemia

Cited by 109 publications

References 8 publications

Eμ/miR-125b transgenic mice develop lethal B-cell malignancies

Eμ/miR-125b transgenic mice develop lethal B-cell malignancies

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

MicroRNA Signatures as Biomarkers in Cancer

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