Involvement of parental imprinting in the antisense regulation of onco-miR-372-373

Stelzer, Yonatan; Sagi, Ido; Benvenisty, Nissim

doi:10.1038/ncomms3724

Cited by 17 publications

(12 citation statements)

References 32 publications

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“…One gene, MEST, showed significant LOI and two genes, H19 and HM13, were borderline significant (FDR < 0.1). MEST is already known to show LOI in varying cancers, including breast cancer and we were here able to confirm this deregulation 21,[30][31][32] . Aberrant H19 imprinting is often seen in cancer as well and is thought to have an important role in cancer development 33,34,21 .…”

Section: Discussionsupporting

confidence: 74%

A Comprehensive Overview of Genomic Imprinting in Breast & Its Deregulation in Cancer

Goovaerts

Steyaert

Vandenbussche

et al. 2018

Preprint

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Genomic imprinting, the parent-of-origin specific monoallelic expression of genes, plays an important role in growth and development. Loss of imprinting of individual genes has been found in varying cancers, yet data-analytical challenges have impeded systematic studies so far. We developed a mixture distribution model to detect monoallelically expressed loci in a genome-wide manner without the need for genotyping data, and applied the methodology on TCGA breast tissue RNA-seq data. We identified 35 putatively imprinted genes in healthy breast. In breast cancer however, HM13 was featured by significant loss of imprinting and expression upregulation, which could be linked to DNA demethylation. Other imprinted genes (25 out of 35) demonstrated consistent expression downregulation in breast cancer, which often correlated with loss of imprinting. A breast imprinted gene network, deregulated in cancer, might hence be present. In summary, our novel methodology highlights the massive deregulation of imprinting in breast cancer.

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Section: Discussionsupporting

confidence: 74%

A Comprehensive Overview of Genomic Imprinting in Breast & Its Deregulation in Cancer

Goovaerts

Steyaert

Vandenbussche

et al. 2018

Preprint

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“…Of note, miR-373 has been previously implicated in several types of cancers as an oncomiR (61), with its downregulation resulting in the growth arrest and the apoptosis of tumor cells (62). Moreover, the increased expression levels of miR-371-5p have been associated with a shorter survival and a poor prognosis of patients with pancreatic cancer (63).…”

Section: Discussionmentioning

confidence: 99%

miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma

et al. 2018

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Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer and is among the leading causes of cancer-related mortality worldwide. Although the dysregulation of microRNAs (miRNAs or miRs) has often been reported in HCC, the precise molecular mechanisms by which miRNAs modulate the process of tumorigenesis and the behavior of cancer cells are not yet clearly understood. In this study, we identified a novel three‑miRNA signature, including miR‑371-5p, miR‑373 and miR‑543, that appears to orchestrate programmed cell necrosis in HCC by directly targeting the caspase‑8 gene (Casp‑8). Our results demonstrated that miR‑371-5p, miR‑373 and miR‑543 were overexpressed in HCC tissues compared with paired adjacent normal tissues. The upregulation of these miRNAs specifically and markedly downregulated the expression of Casp‑8, as well as significantly enhanced the Z-VAD/TNF‑α-induced necroptosis of HCC cells. By contrast, the selective knockdown of miRNA expression led to a significant increase in Casp‑8 levels and a marked reduction in programmed cell necrosis. Intriguingly, the sustained overexpression of Casp‑8 reversed the pro‑necroptotic effects exerted by miRNA mimics. Finally, a strong inverse association between the level of miR‑223 and the expression levels of nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing-3 inflammasome was observed in our HCC specimens. On the whole, the present study revealed a molecular link between the three‑miRNA signature, comprising miR‑371-5p, miR‑373 and miR‑543, and the negative necroptotic regulator Casp‑8, and presents evidence for its employment as a novel potential diagnostic, prognostic and therapeutic target in HCC.

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“…Although the cluster is said to be restricted to eutherian mammals [ 56 ], a cluster of miRNAs adjacent to NLRP12 in the opossum Monodelphis domesticus contains a miRNA with the AAGUGC sequence (miR-1643b-3p). A paternally-expressed, maternally-silent transcript antisense to miR-371~373 has been reported in human pluripotent stem cells [ 57 ].…”

Section: Unimprinted Mirnas With An Aagugc Motifmentioning

confidence: 99%

The Evolution of Imprinted microRNAs and Their RNA Targets

Haig¹,

Mainieri²

2020

Genes

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Mammalian genomes contain many imprinted microRNAs. When an imprinted miRNA targets an unimprinted mRNA their interaction may have different fitness consequences for the loci encoding the miRNA and mRNA. In one possible outcome, the mRNA sequence evolves to evade regulation by the miRNA by a simple change of target sequence. Such a response is unavailable if the targeted sequence is strongly constrained by other functions. In these cases, the mRNA evolves to accommodate regulation by the imprinted miRNA. These evolutionary dynamics are illustrated using the examples of the imprinted C19MC cluster of miRNAs in primates and C2MC cluster in mice that are paternally expressed in placentas. The 3′ UTR of PTEN, a gene with growth-related and metabolic functions, appears to be an important target of miRNAs from both clusters.

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Involvement of parental imprinting in the antisense regulation of onco-miR-372-373

Cited by 17 publications

References 32 publications

A Comprehensive Overview of Genomic Imprinting in Breast & Its Deregulation in Cancer

A Comprehensive Overview of Genomic Imprinting in Breast & Its Deregulation in Cancer

miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma

The Evolution of Imprinted microRNAs and Their RNA Targets

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