Dataset Information

Expression profile analysis of long non-coding RNA in acute myeloid leukemia by microarray and bioinformatics.

ABSTRACT: Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are involved in tumorigenesis and play a key role in cancer progression. To determine whether lncRNAs are involved in acute myeloid leukemia (AML), we analyzed the expression profile of lncRNAs and mRNAs in AML. Five pairs of AML patients and iron deficiency anemia (IDA) controls were screened by microarray. Through coexpression analysis, differently expressed transcripts were divided into modules, and lncRNAs were functionally annotated. We further analyzed the clinical significance of crucial lncRNAs from modules in public data. Finally, the expression of three lncRNAs, RP11-222K16.2, AC092580.4, and RP11-305O.6, were validated in newly diagnosed AML, AML relapse, and IDA patient groups by quantitative RT-PCR, which may be associated with AML patients' overall survival. Further analysis showed that RP11-222K16.2 might affect the differentiation of natural killer cells, and promote the immunized evasion of AML by regulating Eomesodermin expression. Analysis of this study revealed that dysregulated lncRNAs and mRNAs in AML vs IDA controls could affect the immune system and hematopoietic cell differentiation. The biological functions of those lncRNAs need to be further validated.

SUBMITTER: Feng Y

PROVIDER: S-EPMC5797823 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Expression profile analysis of long non-coding RNA in acute myeloid leukemia by microarray and bioinformatics.

Feng Yuandong Y Shen Ying Y Chen Hongli H Wang Xiaman X Zhang Ru R Peng Yue Y Lei Xiaoru X Liu Tian T Liu Jing J Gu Liufang L Wang Fangxia F Yang Yun Y Bai Ju J Wang Jianli J Zhao Wanhong W He Aili A He Aili A

Cancer science 20180127 2

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are involved in tumorigenesis and play a key role in cancer progression. To determine whether lncRNAs are involved in acute myeloid leukemia (AML), we analyzed the expression profile of lncRNAs and mRNAs in AML. Five pairs of AML patients and iron deficiency anemia (IDA) controls were screened by microarray. Through coexpression analysis, differently expressed transcripts were divided into modules, and lncRNAs were functional ...[more]

PMID: 29220122

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Project description:Simple Summary Survival rates for children with acute myeloid leukemia have significantly improved in recent decades. Still, 20–30% will succumb to therapy-related toxicity and relapse. Research has shown that leukemic stem cells (LSCs) in particular are responsible for relapse. Therefore, the characterization of the LSC is needed to improve the current treatment options for and survival of these pediatric patients. Previously, research has focused mainly on the protein-coding part of the human genome, but recently the focus has also shifted to non-coding genes, including long non-coding RNA (lncRNA) and microRNA (miRNA). The aim of this study was to investigate the expression of lncRNAs and miRNAs in pediatric AML subpopulations (LSCs and leukemic blasts) and their normal counterparts (hematopoietic stem cells and control myeloblasts). We provide here a unique set of non-coding RNAs with a potential role in the pathogenesis of pediatric AML, paving the way for further translational research studies. Abstract Pediatric acute myeloid leukemia (pedAML) is a heterogeneous blood cancer that affects children. Although survival rates have significantly improved over the past few decades, 20–30% of children will succumb due to treatment-related toxicity or relapse. The molecular characterization of the leukemic stem cell, shown to be responsible for relapse, is needed to improve treatment options and survival. Recently, it has become clear that non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play a role in the development of human diseases, including pediatric cancer. Nevertheless, non-coding RNA expression data in pedAML are scarce. Here, we explored lncRNA (n = 30,168) and miRNA (n = 627) expression in pedAML subpopulations (leukemic stem cells (LSCs) and leukemic blasts (L-blasts)) and their normal counterparts (hematopoietic stem cells and control myeloblasts). The potential regulatory activity of differentially expressed lncRNAs in LSCs (unique or shared with the L-blast comparison) on miRNAs was assessed. Moreover, pre-ranked gene set enrichment analyses of (anti-) correlated protein-coding genes were performed to predict the functional relevance of the differentially upregulated lncRNAs in LSCs (unique or shared with the L-blast comparison). In conclusion, this study provides a catalog of non-coding RNAs with a potential role in the pathogenesis of pedAML, paving the way for further translational research studies.

Project description:BackgroundGrowing evidence indicates that RNA methylation plays a fundamental role in epigenetic regulation, which is associated with the tumorigenesis and drug resistance. Among them, acute myeloid leukemia (AML), as the top acute leukemia for adults, is a deadly disease threatening human health. Although N7-methylguanosine (m7G) has been identified as an important regulatory modification, its distribution has still remained elusive.MethodsThe present study aimed to explore the long non-coding RNA (lncRNA) functional profile of m7G in AML and drug-resistant AML cells. The transcriptome-wide m7G methylation of lncRNA was analyzed in AML and drug-resistant AML cells. RNA MeRIP-seq was performed to identify m7G peaks on lncRNA and differences in m7G distribution between AML and drug-resistant AML cells. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to predict the possible roles and m7G-associated pathway.ResultsUsing m7G peak sequencing, it was found that a sequence motif was necessary for m7G methylation in drug-resistant AML lncRNA. Unsupervised hierarchical cluster analysis confirmed that lncRNA m7G methylation occurred more frequently in drug-resistant AML cells than in AML cells. RNA sequencing demonstrated that more genes were upregulated by methylation in drug-resistant AML cells, while methylation downregulated more genes in AML cells. The GO and KEGG pathway enrichment analyses revealed that genes having a significant correlation with m7G sites in lncRNA were involved in drug-resistant AML signaling pathways.ConclusionSignificant differences in the levels and patterns of m7G methylation between drug-resistant AML cells and AML cells were revealed. Furthermore, the cellular functions potentially influenced by m7G in drug-resistant AML cells were predicted, providing evidence implicating m7G-mediated lncRNA epigenetic regulation in the progression of drug resistance in AML. These findings highlight the involvement of m7G in the development of drug resistance in AML.

Dataset Information

Expression profile analysis of long non-coding RNA in acute myeloid leukemia by microarray and bioinformatics.

Publications

Expression profile analysis of long non-coding RNA in acute myeloid leukemia by microarray and bioinformatics.

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