Genome-Wide Analysis of Small RNA and Novel MicroRNA Discovery in Human Acute Lymphoblastic Leukemia Based on Extensive Sequencing Approach

Zhang, Hua; Yang, Jianhua; Zheng, Yusheng; Zhang, Peng; Chen, Xiao; Wu, Jun; Xu, Ling; Luo, Xue-Qun; Zhang, Ke; Zhou, Hui; Qu, Liang‐Hu; Chen, Yue‐Qin

doi:10.1371/journal.pone.0006849

Cited by 45 publications

(43 citation statements)

References 53 publications

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“…[32][33][34] In addition, high-throughput sequencing of two libraries compiled of 3 pediatric (genotypically not defined) ALL cases and 2 normal bone marrow samples revealed 42 novel miRNAs of which 5 were unique to ALL and 22 exclusively detected in normal donor bone marrow cells. 35 In a recent study, seven new miRNAs were cloned from AML with normal karyotype. 36 These studies suggest that the number of novel miRNAs being identified is not expected to drastically increase upon additional high-throughput sequencing analyses of similar samples unless the criteria for identification of miRNAs are being altered upon new scientific insights into the structure of miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Discovery of new microRNAs by small RNAome deep sequencing in childhood acute lymphoblastic leukemia

et al. 2011

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MicroRNAs (miRNAs) relevant to acute lymphoblastic leukemia (ALL) in children are hypothesized to be largely unknown as most miRNAs have been identified in non-leukemic tissues. In order to discover these miRNAs, we applied high-throughput sequencing to pooled fractions of leukemic cells obtained from 89 pediatric cases covering seven well-defined genetic types of ALL and normal hematopoietic cells. This resulted into 78 million small RNA reads representing 554 known, 28 novel and 431 candidate novel miR genes. In all, 153 known, 16 novel and 170 candidate novel mature miRNAs and miRNA-star strands were only expressed in ALL, whereas 140 known, 2 novel and 82 candidate novel mature miRNAs and miRNA-star strands were unique to normal hematopoietic cells. Stem-loop reverse transcriptase (RT)-quantitative PCR analyses confirmed the differential expression of selected mature miRNAs in ALL types and normal cells. Expression of 14 new miRNAs inversely correlated with expression of predicted target genes (À0.49p Spearman's correlation coefficients (Rs)pÀ0.27, Pp0.05); among others, low levels of novel sol-miR-23 associated with high levels of its predicted (antiapoptotic) target BCL2 (B-cell lymphoma 2) in precursor B-ALL (Rs À0.36, P ¼ 0.007). The identification of 41000 miR genes expressed in different types of ALL forms a comprehensive repository for further functional studies that address the role of miRNAs in the biology of ALL.

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Section: Discussionmentioning

confidence: 99%

Discovery of new microRNAs by small RNAome deep sequencing in childhood acute lymphoblastic leukemia

et al. 2011

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“…For this reason we and others cloned miRNAs from patient's leukemia cells. 26,28,[63][64][65] Initially, a small RNA concatemer-cloning procedure was used followed by Sanger sequencing and bio-informatic analysis. 26,63 This led to the identification of eight novel miR-genes in MLL-and non-MLL rearranged ALL.…”

Section: Novel Mirnas Potentially Involved In Leukemogenesismentioning

confidence: 99%

“…28 In total, 186 novel (candidate) mature miRNAs and miRNA*-strands were found exclusively in ALL subtypes whereas 84 were found uniquely expressed in normal hematopoietic cells. 28 High-throughput sequencing of 3 pediatric ALL cases and 2 normal bone marrow samples by Zhang et al 65 revealed 42 novel miRNAs of which 5 were unique to ALL and 22 exclusively detected in normal donor bone marrow cells. The differential expression of these newly identified miRNAs between leukemic cells and normal hematopoietic cells warrants further studies for their potential role in leukemogenesis.…”

Section: Novel Mirnas Potentially Involved In Leukemogenesismentioning

confidence: 99%

MicroRNAs in acute leukemia: from biological players to clinical contributors

2011

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MicroRNAs (miRNAs) are involved in the management of hematopoiesis. As a consequence, miRNA dysregulation causes disruption of the hematopoietic system and leukemia may arise. We here comprehensively discuss miRNAs found discriminative for cytogenetic and molecular subtypes of acute leukemia. These miRNAs are either known miRNAs involved in leukemogenesis with proven tumor suppressor or oncogenic activities or are newly identified by high-throughput sequencing with yet unknown function. Furthermore, forces are outlined that drive aberrant miRNA function, which include genetic abnormalities (for example, deletions, translocations and mutations) and epigenetic aberrations (for example, aberrant DNA methylation or histone modifications). Interestingly, leukemia-silenced miRNAs can be re-expressed upon treatment with de-methylating agents. Targeting miRNA expression may serve a therapeutical role, albeit at present this way of targeted therapy is in its infancy. However, emerging knowledge about the biology of miRNAs in leukemia may result into a role for these miRNAs in the diagnosis and treatment of acute leukemia.

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“…One important application of NextGen sequencing technology is the discovery and profiling of small noncoding RNAs (Wei et al 2009;Wyman et al 2009;Zhang et al 2009), including the class known as microRNAs (miRNAs). Mature miRNAs are short RNA molecules (17-25 nucleotides [nt] long) that are processed by the RNase III enzymes, Drosha and Dicer, from transcripts (Davis and Hata 2009;Russo and Giordano 2009).…”

Section: Introductionmentioning

confidence: 99%

Complexity of the microRNA repertoire revealed by next-generation sequencing

Lee¹,

Zhang²,

Etheridge³

et al. 2010

RNA

255

216

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MicroRNAs (miRNAs) have been implicated to play key roles in normal physiological functions, and altered expression of specific miRNAs has been associated with a number of diseases. It is of great interest to understand their roles and a prerequisite for such study is the ability to comprehensively and accurately assess the levels of the entire repertoire of miRNAs in a given sample. It has been shown that some miRNAs frequently have sequence variations termed isomirs. To better understand the extent of miRNA sequence heterogeneity and its potential implications for miRNA function and measurement, we conducted a comprehensive survey of miRNA sequence variations from human and mouse samples using next generation sequencing platforms. Our results suggest that the process of generating this isomir spectrum might not be random and that heterogeneity at the ends of miRNA affects the consistency and accuracy of miRNA level measurement. In addition, we have constructed a database from our sequencing data that catalogs the entire repertoire of miRNA sequences (http://galas.systemsbiology. net/cgi-bin/isomir/find.pl). This enables users to determine the most abundant sequence and the degree of heterogeneity for each individual miRNA species. This information will be useful both to better understand the functions of isomirs and to improve probe or primer design for miRNA detection and measurement.

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Genome-Wide Analysis of Small RNA and Novel MicroRNA Discovery in Human Acute Lymphoblastic Leukemia Based on Extensive Sequencing Approach

Cited by 45 publications

References 53 publications

Discovery of new microRNAs by small RNAome deep sequencing in childhood acute lymphoblastic leukemia

Discovery of new microRNAs by small RNAome deep sequencing in childhood acute lymphoblastic leukemia

MicroRNAs in acute leukemia: from biological players to clinical contributors

Complexity of the microRNA repertoire revealed by next-generation sequencing

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