Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia

Saumet, Anne; Vetter, Guillaume; Bouttier, Manuella; Portales-Casamar, Élodie; Wasserman, Wyeth W.; Maurin, Thomas; Mari, Bernard; Barbry, Pascal; Vallar, Laurent; Friederich, Evelyne; Arar, Khalil; Cassinat, Bruno; Chomienne, Christine; Lecellier, Charles-Henri

doi:10.1182/blood-2008-05-158139

Cited by 100 publications

(101 citation statements)

References 49 publications

(73 reference statements)

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“…Altogether, these results expand and confirm in vivo previous observations obtained in vitro (Garzon et al, 2007;Saumet et al, 2009) and suggest a role of these miRNAs in therapeutic response in APL patients.…”

Section: Differentially Expressed Mirnas In Apl Patients S Careccia Esupporting

confidence: 89%

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

Careccia¹,

Mainardi

Pelosi³

et al. 2009

Oncogene

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MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of critical cell processes such as apoptosis, cell proliferation and differentiation. A small set of miRNAs is differentially expressed in hematopoietic cells and seemingly has an important role in granulopoiesis and lineage differentiation. In this study, we analysed, using a quantitative real-time PCR approach, the expression of 12 granulocytic differentiation signature miRNAs in a cohort of acute promyelocytic leukemia (APL) patients. We found nine miRNAs overexpressed and three miRNAs (miR-107, -342 and let-7c) downregulated in APL blasts as compared with normal promyelocytes differentiated in vitro from CD34 þ progenitors. Patients successfully treated with all-trans-retinoic acid (ATRA) and chemotherapy showed downregulation of miR-181b and upregulation of miR-15b, -16, -107, -223, -342 and let-7c. We further investigated whether the APL-associated oncogene, promyelocytic leukemia gene (PML)/retinoic acid receptor a (RARa), might be involved in the transcriptional repression of miR-107, -342 and let-7c. We found that PML/RARa binds the regulatory sequences of the intragenic miR-342 and let-7c. In addition, we observed, in response to ATRA, the release of PML/ RARa paralleled by their transcriptional activation, together with their host genes, EVL and C21orf34a. In conclusion, we show that a small subset of miRNAs is differentially expressed in APL and modulated by ATRA-based treatment.

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Section: Differentially Expressed Mirnas In Apl Patients S Careccia Esupporting

confidence: 89%

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

Careccia¹,

Mainardi

Pelosi³

et al. 2009

Oncogene

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“…To rank these miRNAs for their potential impact on mRNAs in SNAI1-induced MCF7 cells, we assumed that miRNAs that are central to the regulation of epithelial homeostasis and EMT may target several mRNAs. To narrow down the huge number (up to 500 hits) of in silico predicted target genes of the 26 early up-regulated miRNAs to a list of highconfidence target candidates, we took advantage of the fact that miRNAs destabilize many of their targets (Baek et al, 2008;Saumet et al, 2009). Making use of available time-resolved mRNA profiling data obtained with MCF7-SNAI1 cells , we first established a list of mRNAs whose expression was inversely correlated with that of the up-regulated miRNAs following induction of SNAI1.…”

Section: Resultsmentioning

confidence: 99%

“…Reverse transcription was carried out with random primer (Invitrogen) for mRNA or with specific stem-loop oligonucleotides for miRNA detection as described recently in Saumet et al (2009). Oligonucleotides used for miRNA and mRNA detection are detailed in Supplementary Method 1.…”

Section: Cell Proliferation Analysismentioning

confidence: 99%

miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

et al. 2010

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Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell-cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3 0 -untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our nona priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome.

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“…Notably, miR-23a may produce opposite effects in different types of cancer. For example, miR-23a is downregulated in oral squamous cell carcinoma (OSCC), acute promyelocytic leukemia and colon cancer (10)(11)(12). By contrast, miR-23a is overexpressed in acute lymphoblastic leukemia, glioblastoma and hepatocellular carcinoma (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Upregulation of microRNA-23a regulates proliferation and apoptosis by targeting APAF-1 in laryngeal carcinoma

et al. 2015

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Abstract. ) is a potential biomarker for laryngeal cancer. Apoptotic protease activating factor 1 (APAF-1) was recently demonstrated to be a target of miR-23a. However, whether miR-23a exerts its effects via APAF-1 in laryngeal cancer, remains unknown. In the present study, miR-23a expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). APAF-1 mRNA and protein expression levels were assayed by RT-qPCR and western blotting, respectively. Binding of miR-23a to APAF-1 was monitored by a luciferase reporter assay. Gain-of-function and loss-of-function studies were performed in order to investigate the roles of miR-23a and APAF-1 in Hep2 cell proliferation and apoptosis. miR-23a and APAF-1 were found to be significantly upregulated and downregulated, respectively, in laryngeal cancer tissues, and there was a significant negative correlation between APAF-1 and miR-23a expression. The results of the luciferase reporter assay demonstrated that miR-23a bound directly to the APAF-1 mRNA 3'-untranslated region. Ectopic expression of miR-23a and knockdown of APAF-1 significantly promoted cell proliferation and colony formation, and inhibited early apoptosis in Hep2 cells. In conclusion, miR-23a acts as an oncogenic regulator in laryngeal carcinoma by directly targeting APAF-1, and may be a useful biomarker in the diagnosis and treatment of laryngeal carcinoma.

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Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia

Cited by 100 publications

References 49 publications

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

A restricted signature of miRNAs distinguishes APL blasts from normal promyelocytes

miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

Upregulation of microRNA-23a regulates proliferation and apoptosis by targeting APAF-1 in laryngeal carcinoma

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