ArticleOncogene2014
Therapeutic implications of activation of the host gene (Dleu2) promoter for miR-15a/16-1 in chronic lymphocytic leukemia.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- The Role of MicroRNAs, CircRNAs, and LncRNAs in Chronic Lymphocytic Leukemia.Current pharmaceutical design · 2025Review
- Role of microRNAs in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2023Review
- Research progress in effects of microRNAZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Clinical Significance of microRNAs in Hematologic Malignancies and Hematopoietic Stem Cell Transplantation.Cancers · 2023Review
- Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia.Frontiers in oncology · 2023Review
- The Molecular Mechanisms and Function of miR-15a/16 Dysregulation in Fibrotic Diseases.International journal of molecular sciences · 2022Review
- Circular RNAs in acute myeloid leukemia.Molecular cancer · 2021Review
- Article
- An immunotherapeutic approach to decipher the role of long non-coding RNAs in cancer progression, resistance and epigenetic regulation of immune cells.Journal of experimental & clinical cancer research : CR · 2021Review
- Low miR-16 expression induces regulatory CD4American journal of cancer research · 2021Article
- Long noncoding RNA DLEU2 predicts a poor prognosis and enhances malignant properties in laryngeal squamous cell carcinoma through the miR-30c-5p/PIK3CD/Akt axis.Cell death & disease · 2020Article
- miR-15a-5p, miR-15b-5p, and miR-16-5p inhibit tumor progression by directly targeting MYCN in neuroblastoma.Molecular oncology · 2020Article
- DLEU2 participates in lymphovascular invasion and inhibits cervical cancer cell proliferation, migration, and invasion.International journal of clinical and experimental pathology · 2020Article
- System level characterization of small molecule drugs and their affected long noncoding RNAs.Aging · 2019Article
- Recent Progress on Circular RNA Research in Acute Myeloid Leukemia.Frontiers in oncology · 2019Review
- Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia.Molecular and cellular biology · 2018Article
- Interplay between miRNAs and host genes and their role in cancer.Briefings in functional genomics · 2018Review
- Oncogenic long noncoding RNA landscape in breast cancer.Molecular cancer · 2017Article
- microRNA dependent and independent deregulation of long non-coding RNAs by an oncogenic herpesvirus.PLoS pathogens · 2017Article
- Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA.Genomics, proteomics & bioinformatics · 2017Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Genetic lesions and other regulatory events lead to silencing of the 13q14 locus in a majority of chronic lymphocytic leukemia (CLL) patients. This locus encodes a pair of critical proapoptotic microRNAs, miR-15a/16-1. Decreased levels of miR-15a/16-1 are critical for the increased survival exhibited by CLL cells. Similarly, in a de novo murine model of CLL, the NZB strain, germline-encoded regulation of the syntenic region resulted in decreased miR-15a/16-1. In this paper, we have identified additional molecular mechanisms regulating miR-15a/16-1 levels and have shown that the transcription factor BSAP (B-cell-specific activator protein) directly interacts with Dleu2, the host gene containing the miR-15a/16-1 loci, and by negative regulation of the Dleu2 promoter, results in repression of miR-15a/16-1 expression. CLL patient B-cell expression levels of BSAP were increased compared with control sources of B cells. With the use of small interfering RNA-mediated repression, the levels of BSAP were decreased in vitro in the NZB-derived malignant B-1 cell line, LNC, and in ex vivo CLL patient peripheral blood mononuclear cells (PBMCs). BSAP knockdown led to an increase in the expression of miR-15a/16-1 and an increase in apoptosis, and a cell cycle arrest in both the cell line and patient PBMCs. Moreover, using Dleu2 promoter analysis by chromatin immunoprecipitation assay, we have shown that BSAP directly interacts with the Dleu2 promoter. Derepression of the Dleu2 promoter via inhibition of histone deacetylation combined with BSAP knockdown increased miR-15a/16-1 expression, and also increased malignant B-cell death. In summary, therapy targeting enhanced host gene Dleu2 transcription may augment CLL therapy.
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