A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA

Cesana, Marcella; Cacchiarelli, Davide; Legnini, Ivano; Santini, Tiziana; Sthandier, Olga; Chinappi, Mauro; Tramontano, Anna; Bozzoni, Irene

doi:10.1016/j.cell.2011.10.031

Cited by 280 publications

(354 citation statements)

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“…[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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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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“…Both computational and experimental evidence support the extensive targeting of lncRNAs by miRNAs (Paraskevopoulou et al 2013). While a small number of lncRNAs are currently known to function as ceRNAs (Cesana et al 2011;Fan et al 2013;Wang et al 2013;Tan et al 2014), the full extent of lncRNAs possessing miRNA-dependent regulatory roles remains to be determined (Ulitsky and Bartel 2013).…”

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confidence: 99%

“…Nevertheless, some established ceRNAs neither share an unusually high number of predicted MREs with their mRNA targets nor are especially abundant (Cesana et al 2011;Wang et al 2013), which suggests that other factors, such as miRNA-target affinity or miRNA turnover, might explain their efficient crosstalk. These ceRNAs are also no different from most other lncRNAs (Cabili et al 2011;Derrien et al 2012) with respect to their highly restricted spatial and temporal expression patterns.…”

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confidence: 99%

“…The miRNA-mediated crosstalk among transcripts can involve coding as well as noncoding transcripts, including intergenic long noncoding RNAs (lncRNAs) (Franco-Zorrilla et al 2007;Cesana et al 2011;Wang et al 2013). Thousands of lncRNAs have been annotated in eukaryotic genomes (Derrien et al 2012;Ulitsky and Bartel 2013), many of which are preferentially located in the cytoplasm (van Heesch et al 2014), where they can engage in miRNA-mediated interactions with other transcripts.…”

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confidence: 99%

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Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells

et al. 2015

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Recently, a handful of intergenic long noncoding RNAs (lncRNAs) have been shown to compete with mRNAs for binding to miRNAs and to contribute to development and disease. Beyond these reports, little is yet known of the extent and functional consequences of miRNA-mediated regulation of mRNA levels by lncRNAs. To gain further insight into lncRNA-mRNA miRNA-mediated crosstalk, we reanalyzed transcriptome-wide changes induced by the targeted knockdown of over 100 lncRNA transcripts in mouse embryonic stem cells (mESCs). We predicted that, on average, almost one-fifth of the transcript level changes induced by lncRNAs are dependent on miRNAs that are highly abundant in mESCs. We validated these findings experimentally by temporally profiling transcriptome-wide changes in gene expression following the loss of miRNA biogenesis in mESCs. Following the depletion of miRNAs, we found that >50% of lncRNAs and their miRNA-dependent mRNA targets were up-regulated coordinately, consistent with their interaction being miRNA-mediated. These lncRNAs are preferentially located in the cytoplasm, and the response elements for miRNAs they share with their targets have been preserved in mammals by purifying selection. Lastly, miRNA-dependent mRNA targets of each lncRNA tended to share common biological functions. Post-transcriptional miRNA-mediated crosstalk between lncRNAs and mRNA, in mESCs, is thus surprisingly prevalent, conserved in mammals, and likely to contribute to critical developmental processes.

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“…Individual LncRNA can play an endogenous miRNA sponges to inhibit the expression of miRNA, in turn, to affect some malignant biological behavior of tumor cells . In addition, Cesana has found man and rat skeletal muscle linc-MD1 LncRNA can serve as competing endogenous RNA (ceRNA)to specific bind of miR-133 and miR-135 respectively and indirectly regulate targets of this two miRNAs (Cesana et al, 2011). At present, the study of LncRNA is still in a shallow state that a lot of LncRNAs are undetected or physiological roles are unclear, but the above functions are enough to show, whether direct or indirect, LncRNA is a crucial regulator in life process, including the growth, diseases and even cancer of the organism.…”

Section: Biological Functions Of Long Non-coding Rnasmentioning

confidence: 99%

Functional Roles of Long Non-coding RNA in Human Breast Cancer

Ni¹,

Wang²,

Quan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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A Long Noncoding RNA Controls Muscle Differentiation by Functioning as a Competing Endogenous RNA

Cited by 280 publications

References 0 publications

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

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

Extensive microRNA-mediated crosstalk between lncRNAs and mRNAs in mouse embryonic stem cells

Functional Roles of Long Non-coding RNA in Human Breast Cancer

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