The miR-17∼92 cluster contributes to MLL leukemia through the repression of MEIS1 competitor PKNOX1

Mian, Yousaf A.; Zeleznik‐Le, Nancy J.

doi:10.1016/j.leukres.2016.04.006

Cited by 7 publications

(8 citation statements)

References 45 publications

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“…As shown in Figure A,B; the 3′‐UTR of the Pknox1 mRNA sequence contains two highly conserved target sites of miR‐17 seed family and one conserved target site of miR‐19 seed family. And it has been validated that Pknox1 as a target of both miR‐17 and miR‐19a in a previous study on mixed lineage leukemia . However, the hepatic miR‐19 level was slightly altered in the rat model of T2DM/NAFLD (Figure C).…”

Section: Discussionsupporting

confidence: 57%

MiR‐17 family‐mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling

Lou

Zhang

et al. 2018

J Cellular Molecular Medi

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The aberrant expression of Pknox1 is associated with hepatic glucose and lipid dysmetabolism status of type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism causing Pknox1 overexpression in this pathological status remains unclear. By using miRNA target prediction programs, we found that the 3′‐UTR of the Pknox1 mRNA sequence contains highly conserved target sites of miR‐17 family. In a rat model of streptozotocin and high‐fat diet‐induced T2DM and NAFLD complication, the increased hepatic expression of Pknox1 was consistent with decreased expressions of miR‐17 family, especially miR‐17 and miR‐20a. Furthermore, an inverse correlation was observed between Pknox1 and miR‐17 and miR‐20a in free fatty acids‐induced hepatocyte steatosis. Dual‐luciferase reporter assay further showed that Pknox1 was a valid target gene of miR‐17 family. The ectopic expression of miR‐17 or miR‐20a could markedly suppress Pknox1 expression in hepatocytes. MiR‐17 or miR‐20a overexpression also resulted in significantly enhanced insulin sensitivity and reduced hepatocyte steatosis in HepG2 and L02 cells, which were determined by altered phosphorylation on insulin receptor signaling pathway proteins and decreased intracellular triglyceride and lipid accumulation, respectively. These data implicate the upregulated hepatic expression of Pknox1 in T2DM complicated with NAFLD may be caused by the reduced expression of miR‐17 family, indicating that developing miRNA‐mediated regulation strategies on Pknox1 may provide new therapeutic options for metabolic disease.

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Section: Discussionsupporting

confidence: 57%

MiR‐17 family‐mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling

Lou

Zhang

et al. 2018

J Cellular Molecular Medi

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“…A study on AML cell lines showed that the miR-19a-3p/HIF-1α axis can be targeted by simvastatin, resulting in the regulation of cell invasion, migration, proliferation and apoptosis [ 33 ]. In mixed-lineage leukemia (MLL) cell lines, anti-miR-19a dramatically reduced the colony-forming abilities of MLL cells compared to controls [ 34 ]. Further research and studies into the cellular mechanisms regulated by miR-181a-5p and miR-19a-3p are required in order to elucidate their role in leukemias and their value as potential targets.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Turk

Calin

Kunej

2022

IJMS

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Leukemias are a group of malignancies of the blood and bone marrow. Multiple types of leukemia are known, however reliable treatments have not been developed for most leukemia types. Furthermore, even relatively reliable treatments can result in relapses. MicroRNAs (miRNAs) are a class of short, noncoding RNAs responsible for epigenetic regulation of gene expression and have been proposed as a source of potential novel therapeutic targets for leukemias. In order to identify central miRNAs for leukemia, we conducted data synthesis using two databases: miRTarBase and DISNOR. A total of 137 unique miRNAs associated with 16 types of leukemia were retrieved from miRTarBase and 86 protein-coding genes associated with leukemia were retrieved from the DISNOR database. Based on these data, we formed a visual network of 248 miRNA-target interactions (MTI) between leukemia-associated genes and miRNAs associated with ≥4 leukemia types. We then manually reviewed the literature describing these 248 MTIs for interactions identified in leukemia studies. This manually curated data was then used to visualize a network of 64 MTIs identified in leukemia patients, cell lines and animal models. We also formed a visual network of miRNA-leukemia associations. Finally, we compiled leukemia clinical trials from the ClinicalTrials database. miRNAs with the highest number of MTIs were miR-125b-5p, miR-155-5p, miR-181a-5p and miR-19a-3p, while target genes with the highest number of MTIs were TP53, BCL2, KIT, ATM, RUNX1 and ABL1. The analysis of 248 MTIs revealed a large, highly interconnected network. Additionally, a large MTI subnetwork was present in the network visualized from manually reviewed data. The interconnectedness of the MTI subnetwork suggests that certain miRNAs represent central disease molecules for multiple leukemia types. Additional studies on miRNAs, their target genes and associated biological pathways are required to elucidate the therapeutic potential of miRNAs in leukemia.

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“…In line with our results, previous study found no significant association between miR-17 and NPM1 or FLT3 mutation status in AML patients [ 30 ]. In addition, there was evidence showing that miR-17 ~ 92 cluster contributed to the MEIS1/HOXA9-mediated transformation of MLL leukemia [ 31 ]. MLL is involved in over 100 different recurrent rearrangements, of which greater than 70 translocation partner genes (TPGs) have now been identified [ 32 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of miR-17 predicts adverse prognosis and disease recurrence for acute myeloid leukemia

Zhang

2022

Int J Clin Oncol

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Background The clinical significance of miR-17 in patients with acute myeloid leukemia (AML) remains unknown. Methods Real-time quantitative reverse transcription-polymerase chain reaction (qPCR) was performed to detect the miR-17 expression in 115 de novo AML patients, 31 patients at complete remission (CR) time, 8 patients at relapse time and 30 normal controls. Results MiR-17 was upregulated in de novo AML compared with normal controls. Patients with high expression of miR-17 had less CEBPA double mutation, less favorable ELN-risk and lower CR rate. The level of miR-17 was significantly decreased at CR phase and was returned to primary level even higher when in relapse phase. In addition, Cox regression analysis revealed that miR-17 expression retained independent prognostic significance for overall survival (OS). Moreover, the gene-expression profile analysis of miR-17 in AML obtained from TCGA database was involved in multiple biological functions and signal pathways. Among the differential expressed genes (DEGs), we identified FGL2, PLAUR, SLC2A3, GPR65, CTSS, TLR7, S1PR3, OGFRL1, LILRB1, IL17RA, SIGLEC10, SLAMF7, PLXDC2, HPSE, TCF7 and MYCL as potential direct targets of miR-17 according to in silico analysis. Conclusions High expression of miR-17 in de novo AML patients pointed to dismal clinical outcome and disease recurrence, which could serve as novel prognostic biomarker for AML patients.

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The miR-17∼92 cluster contributes to MLL leukemia through the repression of MEIS1 competitor PKNOX1

Cited by 7 publications

References 45 publications

MiR‐17 family‐mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling

MiR‐17 family‐mediated regulation of Pknox1 influences hepatic steatosis and insulin signaling

MicroRNAs in Leukemias: A Clinically Annotated Compendium

Overexpression of miR-17 predicts adverse prognosis and disease recurrence for acute myeloid leukemia

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