Loss of imprinting and allelic switching at the DLK1-MEG3 locus in human hepatocellular carcinoma

Anwar, S.L.; Krech, T; Hasemeier, Britta; Schipper, Elisa; Schweitzer, Nóra; Vogel, Arndt; Kreipe, HH; Lehmann, Ulrich

doi:10.1055/s-0032-1332046

Cited by 21 publications

(36 citation statements)

References 28 publications

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“…lncRNAs, originally supposed as the “noise” in genome transcription, were gradually emphasized regarding their involvement with OC progression, such as lncRNAs HOST2, NEAT1, HOTAIR, and MEG3 . The MEG3 therein has been extensively investigated as a protector within multifarious neoplasms, such as lung cancer, liver cancer, renal cancer, acute chronic leukemia, and cervical cancer . This antitumor function effect could be driven by the contribution of MEG3 to impeding proliferation and accelerating apoptosis of tumor cells via modulation of certain pathways, such as p53 signaling, Rb/p16INK4A pathway, and Notch signaling .…”

Section: Discussionmentioning

confidence: 99%

lncRNA MEG3 modified epithelial‐mesenchymal transition of ovarian cancer cells by sponging miR‐219a‐5p and regulating EGFR

Wang

Zhao

2019

J of Cellular Biochemistry

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This study was aimed to verify whether there existed any associations between long noncoding RNA MEG3/miR‐219a‐5p/EGFR axis and the development of ovarian cancer (OC). As a whole, we gathered 317 pairs of OC tissues and surgical marginal normal tissues and simultaneously acquired four OC cell lines (ie, A2780, Caov‐3, OVCAR‐3, and SKOV‐3) and human normal ovarian surface epithelial cell line. Moreover, pcDNA3.1‐MEG3, si‐MEG3, miR‐219a‐5p mimic, miR‐219a‐5p inhibitor, pcDNA3.1‐EGFR, and si‐EGFR were, respectively, transfected into the OC cells, and their impacts on viability, proliferation, apoptosis, invasion, and migration of OC cells were assessed via conduction of MTT assay, colony formation assay, flow cytometry assay, transwell assay, and scratch assay. Ultimately, dual‐luciferase reporter gene assay was performed to testify the targeted relationships among maternally expressed gene 3 (MEG3), miR‐219a‐5p, and estimated glomerular filtration rate (EGFR). It was indicated that underexpressed MEG3 and miR‐219a‐5p were significantly associated with unfavorable prognosis of patients with OC when compared with overexpressed MEG3 and miR‐219a‐5p (P < .05). In addition, the OC cells transfected with si‐MEG3 or miR‐219a‐5p inhibitor exhibited stronger viability, proliferation, invasion, and migration than untreated cells (P < .05). Correspondingly, the apoptotic percentage of OC cells was reduced observably under treatments of si‐MEG3 and miR‐219a‐5p inhibitor (P < .05). Moreover, MEG3 exerted modulatory effects on the expression of miR‐219a‐5p (P < .05), and there was a sponging relationship between them (P < .05). Finally, EGFR expression was modified by both MEG3 and miR‐219a‐5p significantly (P < .05), and raising EGFR expression could changeover the impacts of MEG3 and miR‐219a‐5p on the above‐mentioned activity of OC cells (P < .05). Conclusively, MEG3 could serve as a promising biomarker for diagnosis and treatment of OC, considering its involvement with OC etiology via regulation of miR‐219a‐5p/EGFR axis.

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Section: Discussionmentioning

confidence: 99%

lncRNA MEG3 modified epithelial‐mesenchymal transition of ovarian cancer cells by sponging miR‐219a‐5p and regulating EGFR

Wang

Zhao

2019

J of Cellular Biochemistry

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“…Maternally expressed gene 3 (MEG3) is a maternally expressed imprinted gene representing a large non‐coding RNA as its transcript lacks a significant open reading frame . MEG3 is expressed in many normal tissues, however is lost or downregulated in an expanding list of human tumor cell lines and primary tumors . Growing evidence suggests that MEG3 has tumor suppressor properties and is capable of interacting with p53, cyclic AMP, murine double minute 2 (MDM2), and growth differentiation factor 15 (GDF15) to regulate proliferation, migration, and invasion of tumor cells .…”

Section: Introductionmentioning

confidence: 99%

Promoter hypermethylation‐mediated downregulation of miR‐770 and its host gene MEG3, a long non‐coding RNA, in the development of gastric cardia adenocarcinoma

Guo

Zhao

Liu

et al. 2017

Molecular Carcinogenesis

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Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes an lncRNA and is downregulated in an expanding list of cancer cell lines and primary human cancers. The miR-770 is transcribed from the intronic sequence of MEG3 and MEG3 may be the host gene for miR-770. However, the biological role of MEG3 and miR-770 in gastric cardia adenocarcinoma (GCA) development and prognosis is poorly defined. The present study was to investigate the function and methylation status of MEG3 in GCA, and further to detect the functional association of miR-770 and its host gene MEG3 in GCA carcinogenesis and prognosis. MEG3 and miR-770 was significantly downregulated in GCA patients and cell lines, and their expression was associated with TNM stage and lymph node metastasis. Overexpression of MEG3 and miR-770 inhibited gastric cancer cell proliferation and invasion in vitro. Furthermore, the expression level of MEG3 and miR-770 was significantly increased in cancer cells after treated with 5-Aza-dC. The aberrant hypermethylation of proximal promoter and enhancer region of MEG3 was detected in GCA tissues. In addition, the proximal promoter and enhancer region hypermethylation and dysregulation of MEG3 and miR-770 were associated with poorer GCA patients' survival. These findings suggest that miR-770 and its host gene MEG3 may play tumor suppressor role and hypermethylation of proximal promoter and enhancer region may be one of the critical mechanisms in inactivation of MEG3 and miR-770 in GCA development. MEG3 and miR-770 may be used as potential biomarkers in predicting GCA patients' prognosis.

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“…The relative expression is presented as the fold-change on a log scale. Samples were classified as 'high-expression' if the lower limit of the log value was >1, as 'low-expression' if the upper limit was <1 but >0, and as 'lost expression' if the upper limit was <0(14).Compared with the normal samples, of which 85% (17 of 20) were 'high-expression', 5% (1 of 20) of the cancer samples were 'high-expression', 25% (5 of 20) were 'low-expression' and 70% (14 of 20) were 'lost expression' (P<0.01). MEG3, maternally expressed 3; EOC, epithelial ovarian cancer.…”

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confidence: 99%

Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer

Sheng

Yang

et al. 2014

Oncology Reports

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Maternally expressed 3 (MEG3) is a long non-coding RNA that can activate p53 and inhibit tumorigenesis and progression of various types of cancers. However, the role of MEG3 in epithelial ovarian cancer (EOC) is still unknown. The aim of the present study was to confirm whether MEG3 is downregulated in human EOC, determine its possible mechanism of action and elucidate the role of MEG3 in EOC. Differences in the expression of MEG3 and in the methylation status of the MEG3 promoter between EOC and normal ovary were analyzed using RT-PCR and methylation-specific PCR (MSP), respectively. MTT and EdU assays and flow cytometric analysis were used to assess the growth of ovarian cancer cells after overexpression of MEG3. The target genes regulated by MEG3 were detected with the Dual Luciferase Reporter system. The expression levels of target genes were confirmed using RT-PCR and western blotting. In contrast to normal ovarian tissues, the expression of MEG3 was absent or decreased in most EOC tissues as well as in human EOC cell lines, and the promoter of the MEG3 gene was highly methylated in both cancer tissues and cell lines. Treatment with 5-aza-2-deoxycytidine reversed the promoter hypermethylation and increased MEG3 expression. In addition, ectopic expression of MEG3 suppressed the proliferation and growth of OVCAR3 cells and promoted apoptosis. Finally, MEG3 activated p53 in OVCAR3 cells. In conclusion, our data suggest that MEG3 is epigenetically silenced in EOC due to promoter hypermethylation, which may contribute to the development of EOC.

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Loss of imprinting and allelic switching at the DLK1-MEG3 locus in human hepatocellular carcinoma

Cited by 21 publications

References 28 publications

lncRNA MEG3 modified epithelial‐mesenchymal transition of ovarian cancer cells by sponging miR‐219a‐5p and regulating EGFR

lncRNA MEG3 modified epithelial‐mesenchymal transition of ovarian cancer cells by sponging miR‐219a‐5p and regulating EGFR

Promoter hypermethylation‐mediated downregulation of miR‐770 and its host gene MEG3, a long non‐coding RNA, in the development of gastric cardia adenocarcinoma

Promoter hypermethylation influences the suppressive role of maternally expressed 3, a long non-coding RNA, in the development of epithelial ovarian cancer

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