miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells

Zhang, Hongmei; Li, Qing; Zhu, Xiaojian; Liu, Wei; Hu, Hui; Li, Teng; Cheng, Fanjun; You, Yong; Zhong, Zhaodong; Zou, Ping; Li, Qiubai; Chen, Zhichao; Guo, An‐Yuan

doi:10.1158/0008-5472.can-15-2120

Cited by 85 publications

(48 citation statements)

References 48 publications

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“…MiR-146b was also reported to be a differential expression miRNA between M1 and M5 FAB subtypes, and was speculated participating in the block of M1 development and maturation, although its further function was not studied in AML [12]. It was found to play an oncogenic role in hematologic malignancies including T-ALL and lymphoma [19, 20], and to promote leukemic transformation of hematopoietic cells within BCR-ABL1-positive microvesicles [21]. MiR-146b is a key regulator accelerated the transformation by targeting NUMB and other genes, causing genome instability [20].…”

Section: Discussionmentioning

confidence: 99%

A 3-miRNA signature predicts prognosis of pediatric and adolescent cytogenetically normal acute myeloid leukemia

et al. 2017

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Acute myeloid leukemia is a hematologic malignancy with significant molecular heterogeneity. MicroRNAs have important biological functions and play critical roles in pathogenesis and prognosis in a variety of cancers including acute myeloid leukemia. Some reports have constructed risk stratification systems for adult acute myeloid leukemia patients using microRNAs to predict an optimal outcome of patients. However, little has been done in pediatric and adolescent patients. The purpose of this study is to identify a panel of microRNA signature that could predict prognosis in younger cytogenetically normal acute myeloid leukemia patients by analyzing the data from The Cancer Genome Atlas. A total of 59 cytogenetically normal acute myeloid leukemia patients under 21 years with corresponding clinical data were enrolled in our study. Using univariate Cox's model, we found 17 miRNAs were significantly related with overall survival in pediatric and adolescent cytogenetically normal acute myeloid leukemia patients but no clinical parameter was found significant related with overall survival. The multivariate Cox regression identified high expression of hsa-miR-146b was independent poor prognostic factor and high expression of hsa-miR-181c and hsa-miR-4786 appeared to be favorable factors. A model was proposed based on these three miRNAs. Leave-one-out Cross Validation method and Permutation Test was further used to evaluate this model. The function role of has-mir-181c was further studied by carrying out flow cytometry and cell counting kit-8 (CCK-8) in U937 cell line. The results indicate that the 3-microRNA-based signature is a reliable prognostic biomarker for pediatric and adolescent cytogenetically normal acute myeloid leukemia patients.

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Section: Discussionmentioning

confidence: 99%

A 3-miRNA signature predicts prognosis of pediatric and adolescent cytogenetically normal acute myeloid leukemia

et al. 2017

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“…The K562-MVs small RNA-seq data were from our previous findings [33]. The FASTQ files of the RNA-Seq and small RNA-Seq data of RPMI8226-MVs and K562-MVs were submitted to the NCBI Sequence Read Archive (SRA) under accession numbers SRP092289 and SRP057826, respectively.…”

Section: Methodsmentioning

confidence: 99%

Tumor Cell-Derived Microvesicles Induced Not Epithelial-Mesenchymal Transition but Apoptosis in Human Proximal Tubular (HK-2) Cells: Implications for Renal Impairment in Multiple Myeloma

Zhao

Kong

Liu

et al. 2017

IJMS

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Renal impairment (RI) is one of the hallmarks of multiple myeloma (MM) and carries a poor prognosis. Microvesicles (MVs) are membrane vesicles and play an important role in disease progression. Here, we investigated the role of MVs derived from MM cells (MM-MVs) in RI of MM. We found that MM-MVs significantly inhibited viability and induced apoptosis, but not epithelial-mesenchymal transition in human kidney-2 (HK-2), a human renal tubular epithelial cell line. The protein levels of cleaved caspase-3, 8, and 9, and E-cadherin, were increased, but vementin levels were decreased in the HK-2 cells treated with MM-MVs. Through a comparative sequencing and analysis of RNA content between the MVs from RPMI8226 MM cells (RPMI8226-MVs) and K562 leukemia cells, RPMI8226-MVs were enriched with more renal-pathogenic miRNAs, in which the selective miRNAs may participate in the up-regulation of the levels of cleaved caspase-3. Furthermore, the levels of CD138+ circulating MVs (cirMVs) in the peripheral blood were positively correlated with the severity of RI in newly-diagnosed MM. Our study supports MM-MVs representing a previously undescribed factor and playing a potential role in the development of RI of MM patients, and sheds light on the potential application of CD138+ cirMV counts in precise diagnosis of RI in MM and exploring MM-MVs as a therapeutic target.

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“…We intersected predicted miRNA targets from TargetScan and miRanda, and unioned verified miRNA targets from TarBase, miRTarBase, miR2Disease, miRecords, miRwalk to get the final miRNA-target result as our previous studies [42, 43]. Gene sets of signaling pathways were obtained from the Cancer Genome Anatomy Project database (http://cgap.nci.nih.gov/Pathways/BioCarta_Pathways).…”

Section: Methodsmentioning

confidence: 99%

MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-β pathway via targeting SMAD3

Huang

et al. 2016

Oncotarget

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MicroRNAs (miRNAs) are non-coding RNAs with functions of posttranscriptional regulation. The abnormally expressed miRNAs have been shown to be crucial contributors and may serve as biomarkers in many diseases. However, determining the biological function of miRNAs is an ongoing challenge. By combining miRNA targets prediction, miRNA and mRNA expression profiles in TCGA cancers, and pathway data, we performed a miRNA-pathway regulation inference by Fisher's exact test for enrichment analysis. Then we constructed a database to show the cancer related miRNA-pathway regulatory network (http://bioinfo.life.hust.edu.cn/miR_path). As one of the miRNAs targeting many cancer related pathways, miR-142-5p potentially regulates the maximum number of genes in TGF-β signaling pathway. We experimentally confirmed that miR-142-5p directly targeted and suppressed SMAD3, a key component in TGF-β signaling. Ectopic overexpression of miR-142-5p significantly promoted tumor cell proliferation and inhibited apoptosis, while silencing of miR-142-5p inhibited the tumor cell proliferation and promoted apoptosis in vitro. These findings indicate that miR-142-5p plays as a negative regulator in TGF-β pathway by targeting SMAD3 and suppresses TGF-β-induced growth inhibition in cancer cells. Our study proved the feasibility of miRNA regulatory pathway analysis and shed light on combining bioinformatics with experiments in the research of complex diseases.

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miR-146b-5p within BCR-ABL1–Positive Microvesicles Promotes Leukemic Transformation of Hematopoietic Cells

Cited by 85 publications

References 48 publications

A 3-miRNA signature predicts prognosis of pediatric and adolescent cytogenetically normal acute myeloid leukemia

A 3-miRNA signature predicts prognosis of pediatric and adolescent cytogenetically normal acute myeloid leukemia

Tumor Cell-Derived Microvesicles Induced Not Epithelial-Mesenchymal Transition but Apoptosis in Human Proximal Tubular (HK-2) Cells: Implications for Renal Impairment in Multiple Myeloma

MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-β pathway via targeting SMAD3

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