The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Bao, Xichen; Wu, Hao; Xihua, Zhu; Guo, Xiangpeng; Hutchins, Andrew P.; Luo, Zhiwei; Sui, Hong; Chen, Yongqiang; Lai, Keyu; Yin, Menghui; Xu, Lingxiao; Zhou, Liang; Chen, Jiekai; Wang, Dongye; Qin, Baoming; Frampton, Jon; Tse, Hung‐Fat; Pei, Duanqing; Wang, Huating; Zhang, Biliang; Esteban, Miguel A.

doi:10.1038/cr.2014.165

Cited by 164 publications

(138 citation statements)

References 40 publications

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“…This is due to the fact that biochemical and in vitro studies have shown that hnRNP K has the capacity to regulate both tumor suppressive and oncogenic pathways, and both its overexpression and knockdown results in cell proliferation and apoptotic defects. [8][9][10][11][12][13] In support of its potential oncogenic functions, clinical association studies suggest that hnRNP K overexpression correlates with poor clinical outcomes and advanced disease status in a variety of malignancies, including melanoma, prostate, breast, lung, colorectal, hepatocellular, and esophageal cancers. [14][15][16][17][18] In contrast, other clinical studies suggest reduced hnRNP K expression, due to deletion of or mutations in the HNRNPK gene, may underpin the pathogenesis of acute myeloid leukemia (AML).…”

Section: Introductionmentioning

confidence: 99%

Aberrant hnRNP K expression: All roads lead to cancer

et al. 2016

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The classification of a gene as an oncogene or a tumor suppressor has been a staple of cancer biology for decades. However, as we delve deeper into the biology of these genes, this simple classification has become increasingly difficult for some. In the case of heterogeneous nuclear ribonuclear protein K (hnRNP K), its role as a tumor suppressor has recently been described in acute myeloid leukemia and demonstrated in a haploinsufficient mouse model. In contrast, data from other clinical correlation studies suggest that hnRNP K may be more fittingly described as an oncogene, due to its increased levels in a variety of malignancies. hnRNP K is a multifunctional protein that can regulate both oncogenic and tumor suppressive pathways through a bevy of chromatin-, DNA-, RNA-, and protein-mediated activates, suggesting its aberrant expression may have broad-reaching cellular impacts. In this review, we highlight our current understanding of hnRNP K, with particular emphasis on its apparently dichotomous roles in tumorigenesis.

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Section: Introductionmentioning

confidence: 99%

Aberrant hnRNP K expression: All roads lead to cancer

et al. 2016

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“…lncRNAs have dynamic effects in transcriptional regulation, and are involved in several human diseases, particularly cancer (52). For example, lincRNA-p21 prevents reprogramming by sustaining CpG methylation of pluripotency gene promoters (32). The present study investigated the potential roles of RP5-833A20.1 in methylation.…”

Section: Discussionmentioning

confidence: 99%

“…A B C during the development of disease (11,32,33). To assess the role of RP5-833A20.1 in the regulation of DNA methylation, the present study assessed the methylation level of the NFIA gene promoter using BSP.…”

mentioning

confidence: 99%

Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells

Kang

Nie

et al. 2016

Molecular Medicine Reports

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Abstract. Early reports suggest that nuclear factor IA (NFIA) is important in the pathogenesis of glioma. Our previous study demonstrated that the long non-coding RNA (lncRNA), RP5-833A20.1, suppressed the expression of NFIA in THP-1 macrophage-derived foam cells. However, the effect and possible mechanism of RP5-833A20.1 on glioma remains to be fully elucidated, and whether the NFIA-dependent pathway is involved in its progression has not been investigated. In the present study, the mechanisms by which RP5-833A20.1 regulates the expression of NFIA in glioma were investigated. The expression levels of RP5-833A20.1 and NFIA were determined in U251 cells and clinical samples using reverse transcription-quantitative polymerase chain reaction (PCR) analysis. The effects of RP5-833A20.1 on cell proliferation, invasion, cell cycle and apoptosis were evaluated using in vitro assays. The potential changes in protein expression were investigated using western blot analysis. The methylation status of the CpG island in the NFIA promoter was determined using bisulfite PCR (BSP) sequencing. It was found that the expression of RP5-833A20.1 was downregulated, whereas the expression of NFIA was upregulated in glioma tissues, compared with corresponding adjacent nontumor tissues from 20 patients with glioma. The overexpression of RP5-833A20.1 inhibited proliferation and cell cycle progression, and induced apoptosis in the U251 cells. The mRNA and protein levels of NFIA were markedly inhibited by overexpression of RP5-833A20.1 in the U251 cells. The overexpression of RP5-833A20.1 increased the expression of microRNA-382-5p in the U251 cells. The BSP assay revealed that the overexpression of RP5-833A20.1 enhanced the methylation level of the NFIA promoter. These results demonstrated that RP5-833A20.1 inhibited tumor cell proliferation, induced apoptosis and inhibited cell-cycle progression by suppressing the expression of NFIA in U251 cells. Collectively, these results indicated RP5-833A20.1 as a novel therapeutic target for glioma.

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“…In iPSC, lincRNA‐p21 prevented reprogramming by activating epigenetic markers to induce heterochromatin at pluripotency gene promoters 80. Moreover, lincRNA‐p21 is down‐regulated in many types of cancer, including gliomas and GSCs, behaving as a tumour suppressor.…”

Section: Tumour‐suppressor Lncrnasmentioning

confidence: 99%

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

Pop

Enciu

Necula

et al. 2018

J Cellular Molecular Medi

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Glioma biology is a major focus in tumour research, primarily due to the aggressiveness and high mortality rate of its most aggressive form, glioblastoma. Progress in understanding the molecular mechanisms behind poor prognosis of glioblastoma, regardless of treatment approaches, has changed the classification of brain tumours after nearly 100 years of relying on anatomopathological criteria. Expanding knowledge in genetic, epigenetic and translational medicine is also beginning to contribute to further elucidating molecular dysregulation in glioma. Long non‐coding RNAs (lncRNAs) and their main representatives, large intergenic non‐coding RNAs (lincRNAs), have recently been under scrutiny in glioma research, revealing novel mechanisms of pathogenesis and reinforcing others. Among those confirmed was the reactivation of events significant for foetal brain development and neuronal commitment. Novel mechanisms of tumour suppression and activation of stem‐like behaviour in tumour cells have also been examined. Interestingly, these processes involve lncRNAs that are present both during normal brain development and in brain malignancies and their reactivation might be explained by epigenetic mechanisms, which we discuss in detail in the present review. In addition, the review discusses the lncRNAs‐induced changes, as well as epigenetic changes that are consequential for tumour formation, affecting, in turn, the expression of various types of lncRNAs.

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The p53-induced lincRNA-p21 derails somatic cell reprogramming by sustaining H3K9me3 and CpG methylation at pluripotency gene promoters

Cited by 164 publications

References 40 publications

Aberrant hnRNP K expression: All roads lead to cancer

Aberrant hnRNP K expression: All roads lead to cancer

Long non-coding RNA RP5-833A20.1 inhibits proliferation, metastasis and cell cycle progression by suppressing the expression of NFIA in U251 cells

Long non‐coding RNAs in brain tumours: Focus on recent epigenetic findings in glioma

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