Ultraconserved Regions Encoding ncRNAs Are Altered in Human Leukemias and Carcinomas

Calin, George A.; Liu, Chang Gong; Ferracin, Manuela; Hyslop, Terry; Spizzo, Riccardo; Sevignani, Cinzia; Fabbri, Muller; Cimmino, Amelia; Lee, Eun Joo; Wojcik, Sylwia E.; Shimizu, Masayoshi; Tili, Esmerina; Rossi, Simona; Taccioli, Cristian; Pichiorri, Flavia; Liu, Xiuping; Zupo, Simona; Herlea, Vlad; Gramantieri, Laura; Lanza, Giovanni; Alder, Hansjüerg; Rassenti, Laura Z.; Volinia, Stefano; Schmittgen, Thomas D.; Kipps, Thomas J.; Negrini, Massimo; Croce, Carlo M.

doi:10.1016/j.ccr.2007.07.027

Cited by 681 publications

(822 citation statements)

References 51 publications

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“…Increasing evidence suggests that these regions may be differentially expressed in human lymphomas and carcinomas (Calin et al., 2007). CGI hypermethylation suppresses the expression of the ultra‐conserved regions, which is not uncommon in human cancers (Lujambio et al., 2010).…”

Section: Discussionmentioning

confidence: 99%

Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction

2018

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SummaryAging is characterized by numerous molecular changes, such as accumulation of molecular damage and altered gene expression, many of which are linked to DNA methylation. Here, we characterize the blood DNA methylome across 16 age groups of mice and report numerous global, region‐ and site‐specific features, as well as the associated dynamics of methylation changes. Transition of the methylome throughout lifespan was not uniform, with many sites showing accelerated changes in late life. The associated genes and promoters were enriched for aging‐related pathways, pointing to a fundamental link between DNA methylation and control of the aging process. Calorie restriction both shifted the overall methylation pattern and was accompanied by its gradual age‐related remodeling, the latter contributing to the lifespan‐extending effect. With age, both highly and poorly methylated sites trended toward intermediate levels, and aging was accompanied by an accelerated increase in entropy, consistent with damage accumulation. However, the entropy effects differed for the sites that increased, decreased and did not change methylation with age. Many sites trailed behind, whereas some followed or even exceeded the entropy trajectory and altered the developmental DNA methylation pattern. The patterns we observed in certain genomic regions were conserved between humans and mice, suggesting common principles of functional DNA methylome remodeling and its critical role in aging. The highly resolved DNA methylome remodeling provides an excellent model for understanding systemic changes that characterize the aging process.

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Section: Discussionmentioning

confidence: 99%

Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction

2018

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“…In the case of CRC, the administration of specific siRNAs targeting the oncogenic HOTAIR, CCAT2, and uc.73a transcripts was shown to decrease the invasion or proliferation of colon cancer cells. 20,58,62 Although the results presented in these studies are only preliminary in vitro data, these reports suggest that RNAi-based therapy strategies are amenable to further development, particularly for cellular therapies.…”

Section: Tumor Treatmentmentioning

confidence: 94%

“…[59][60][61][62] Previous investigations revealed that an effector lncRNA downstream of TP53-LOC285194, also referred to as tumor-suppressor candidate 7-is significantly deregulated in CRC 63 and can suppress tumor cell growth both in vitro and in vivo. 64,65 Exon 4 of LOC285194, which is responsible for tumor cell growth inhibition, contains an active region that harbors two MIR211 binding sites.…”

Section: Role Of Lncrnas In Tumorigenesis and Progressionmentioning

confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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“…miRNAs can block mRNA translation and affect both the expression of protein-coding genes 21 and long ncRNAs. 22 A growing number of reports have been showing that miRNAs are master regulators of important gene networks in eukaryotic cells. 23 Associations of deregulated expression of miRNAs in complex diseases have been also described (for review see Gartel and Kandel 24 ).…”

Section: New Players In Pharmacogenomicsmentioning

confidence: 99%

“…34 There is also evidence that miRNAs can regulate the expression of large ncRNAs, indicating that these small genes have a big impact in transcriptome networks in eukaryotic cells. 22 Several groups studying the biology of miRNAs have been able to describe each step in the processing and mechanism of action of these regulators. It is already known that they are initially transcribed as pri-miRNAs which can be processed into premiRNAs and subsequently into mature miRNAs.…”

Section: Micrornasmentioning

confidence: 99%

The impact of microRNAs and alternative splicing in pharmacogenomics

2009

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Ultraconserved Regions Encoding ncRNAs Are Altered in Human Leukemias and Carcinomas

Cited by 681 publications

References 51 publications

Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction

Global remodeling of the mouse DNA methylome during aging and in response to calorie restriction

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

The impact of microRNAs and alternative splicing in pharmacogenomics

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