Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A

Kaymaz, Burçin Tezcanlı; Günel, Nur Selvi; Ceyhan, Metin; Çetintaş, Vildan Bozok; Özel, Buket; Yandım, Melis Kartal; Kıpçak, Sezgi; Aktan, Çağdaş; Gökbulut, Aysun Adan; Baran, Yusuf; Can, Buket Kosova

doi:10.1007/s13277-015-3509-9

Cited by 22 publications

(15 citation statements)

References 25 publications

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“…They also had target miRNAs, such as miR-744-5p, miR-1538, miR-2278, miR-3687 and they were gradually found to play an important role in the life process. [37][38][39][40] Then we evaluated the expression of these three circRNAs in plasma to be regarded as potential biomarkers for prediction of PE, among which the expression data of circRNA_3286 might serve as a candidate potential biomarker for diagnosis of PE. In recent years, more and more studies indicated that the abnormal recasting of spiral arteries and the defect of trophoblast cell invasion play an important role in the pathogenesis of PE.…”

Section: Discussionmentioning

confidence: 99%

The profile analysis of circular RNAs in human placenta of preeclampsia

Zhou¹,

Wang²,

Wu³

et al. 2018

Exp Biol Med (Maywood)

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A total of 70 pregnant women were recruited for this study, including 35 early onset preeclampsia (PE) and 35 normal pregnant women. By RNA sequencing, the circular RNA (circRNAs) in placenta were identified. Differentially expressed circRNAs were bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of Genes and Genomes, and circRNA–miRNA interaction prediction. Quantitative real time polymerase chain reaction(qRT-PCR) assay was used to verify the results. Compared with the normal pregnant women, there were 49 circRNAs differentially expressed in the placental tissue of PE women, including two circRNAs were up-regulated and 47 were down-regulated. Ten differentially expressed circRNAs were selected for validation by qRT-PCR, among which results of three circRNAs, circRNA_3286, circRNA_5593, and circRNA_3800, were consistent with the sequencing. According to the bioinformatic prediction, we speculate that these circRNAs may be involved in some cellular regulatory functions in PE through their targeted miRNAs. We also evaluated the expression of circRNA_3286 in plasma to be used as a potential biomarker for PE; in vitro Transwell assay shown transfected with si-circ-3286 significantly reduced invasion in HTR8/Svneo cells. In conclusion, we displayed a preliminary landscape of circRNA differential expression in PE and discussed their possible regulatory mechanisms. This study revealed a new insight into the molecular mechanism of PE. Impact statement The abnormal expression of many regulatory factors may be involved in the development of PE. circRNAs are proved to have a series of important biological functions; however, reports about circRNA and PE are rare. In this work, we evaluated the profile analysis of circRNAs in human placenta of PE by RNA-seq and found some newly differentially expressed circRNAs which might be involved in PE. Combined with bioinformatics analysis, their possible functions were preliminarily discussed.

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Section: Discussionmentioning

confidence: 99%

The profile analysis of circular RNAs in human placenta of preeclampsia

Zhou¹,

Wang²,

Wu³

et al. 2018

Exp Biol Med (Maywood)

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“…We identified differentially‐expressed miRNAs among children with severe and mild SCA compared to healthy children; in particular, 3 miRNAs that are exclusively represented in severe‐SCA patients and 141 miRNAs that are exclusively identified in mild‐SCA patients, enabling us to explore their putative gene target pathways and functions, which include cellular growth, proliferation, metabolism and movement. Of note, among the 3 unique miRNAs in EV of severe‐SCA patients, hsa‐mir‐124‐3p is altered during exacerbations of Crohn's disease (Guo et al , ), whereas hsa‐mir‐2278 was predicted as a tumour suppressor (Kaymaz et al , ).There was no information available for hsa‐mir‐4763‐5p, with gene target predictions consisting of 224 genes on the TargetScan database that include thyroid hormone (hsa04919; P ‐value <0·0002) and PPAR signalling pathways (hsa03320; P ‐value <0·0003).…”

Section: Discussionmentioning

confidence: 99%

Extracellular microvesicle microRNAs in children with sickle cell anaemia with divergent clinical phenotypes

et al. 2016

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Sickle cell anaemia (SCA) is the most frequent genetic haemoglobinopathy, which exhibits a highly variable clinical course characterized by hyper-coagulable and pro-inflammatory states, as well as endothelial dysfunction. Extracellular microvesicles are released into biological fluids and play a role in modifying the functional phenotype of target cells. We hypothesized that potential differences in plasma-derived extracellular microvesicles (EV) function and cargo from SCA patients may underlie divergent clinical trajectories. Plasma EV from SCA patients with mild, intermediate and severe clinical disease course were isolated, and primary endothelial cell cultures were exposed. Endothelial cell activation, monocyte adhesion, barrier disruption and exosome cargo (microRNA microarrays) were assessed. EV disrupted the endothelial barrier and induced expression of adhesion molecules and monocyte adhesion in a SCA severity-dependent manner compared to healthy children. Microarray approaches identified a restricted signature of exosomal microRNAs that readily distinguished severe from mild SCA, as well as from healthy children. The microRNA candidates were further validated using quantitative real time polymerase chain reaction assays, and revealed putative gene targets. Circulating exosomal microRNAs may play important roles in predicting the clinical course of SCA, and in delineation of individually tailored, mechanistically-based clinical treatment approaches of SCA patients in the near future.

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“…Up‐regulation of miR‐2278 expression leads to inhibition of the proliferation of resistant leukemia cells and induction of apoptosis. AKT2 inhibits leukemia cell proliferation and induces apoptosis upon experimental verification (Kaymaz et al, ). The BCL6 proto‐oncogene is a key effector of FoxO in self‐renewing signaling in CML‐initiating cells and inhibits Arf and p53 in CML cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of key candidate targets and pathways for the targeted treatment of leukemia stem cells of chronic myelogenous leukemia using bioinformatics analysis

Liu

Zhuang

et al. 2019

Molec Gen & Gen Med

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Background Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm that arises from the acquisition of constitutively active BCR‐ABL tyrosine kinase in hematopoietic stem cells. The persistence of bone marrow leukemia stem cells (LSCs) is the main cause of TKI resistance and CML relapse. Therefore, finding a key target or pathway to selectively target LSCs is of great significance for the thorough treatment of CML. Methods In this study, we aimed to identify key microRNAs, microRNA targets and pathways for the treatment of CML LSCs by integrating analyses of three microarray data profiles. We identified 51 differentially expressed microRNAs through integrated analysis of GSE90773 and performed functional gene predictions for microRNAs. Then, GSE11889 and GSE11675 were integrated to obtain differentially expressed genes (DEGs), and the overlapping DEGs were used as models to identify predictive functional genes. Finally, we identified 116 predictive functional genes. Clustering and significant enrichment analysis of 116 genes was based on function and signaling pathways. Subsequently, a protein interaction network was constructed, and module analysis and topology analysis were performed on the network. Results A total of 11 key candidate targets and 33 corresponding microRNAs were identified. The key pathways were mainly concentrated on the PI3K/AKT, Ras, JAK/STAT, FoxO and Notch signaling pathways. We also found that LSCs negatively regulated endogenous and exogenous apoptotic pathways to escape from apoptosis. Conclusion We identified key candidate targets and pathways for CML LSCs through bioinformatics methods, which improves our understanding of the molecular mechanisms of CML LSCs. These candidate genes and pathways may be therapeutic targets for CML LSCs.

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Revealing genome-wide mRNA and microRNA expression patterns in leukemic cells highlighted “hsa-miR-2278” as a tumor suppressor for regain of chemotherapeutic imatinib response due to targeting STAT5A

Cited by 22 publications

References 25 publications

The profile analysis of circular RNAs in human placenta of preeclampsia

The profile analysis of circular RNAs in human placenta of preeclampsia

Extracellular microvesicle microRNAs in children with sickle cell anaemia with divergent clinical phenotypes

Identification of key candidate targets and pathways for the targeted treatment of leukemia stem cells of chronic myelogenous leukemia using bioinformatics analysis

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