Long Noncoding RNA MEG3 Interacts with p53 Protein and Regulates Partial p53 Target Genes in Hepatoma Cells

Zhu, Juanjuan; Liu, Shanshan; Ye, Fuqiang; Shen, Yuan; Tao, Yi; Zhu, Jie; Wei, Lixin; Jin, Yinghua; Fu, Hanjiang; Wu, Yongge; Zheng, Xiaofei

doi:10.1371/journal.pone.0139790

Cited by 138 publications

(128 citation statements)

References 41 publications

(35 reference statements)

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“…Kai-hua et al claimed that MEG3 inhibits NSCLC cell proliferation and induces apoptosis by affecting p53 expression (19). Zhu et al indicated that MEG3 interacts with p53 protein and regulates p53 target genes in hepatoma cells (20). We detected the expression of p53 in MG63 cells before and after transfection, and discovered that the expression level of p53 also increased after MEG3 up-regulation.…”

Section: Discussionmentioning

confidence: 80%

“…MEG3 is expressed in many human normal tissues, but has failed to express in a variety of human tumour cells, such as non-small cell lung cancer, bladder cancer, prostate cancer and other cancers (9)(10)(11)(12)(13)(14). Additionally, many studies have articulated that MEG3 gene plays an inhibiting role in various tumour cells (15)(16)(17)(18)(19)(20). However, the functional mechanism of MEG3 in MG63 has yet to be proven.…”

Section: Introductionmentioning

confidence: 99%

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MEG3 inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells

Shi

2017

Oncol Lett

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Abstract.Osteosarcoma is known as a malignant tumour with a high mortality rate in orthopaedic settings; however, the factors associated with its degree of malignancy and the biological response remains to be elucidated. Although the essential role of the long noncoding RNA (lncRNA) maternally expressed 3 (MEG3) has been recently reported, its biological functions and regulatory mechanism in osteosarcoma cells have not yet been reported. In the present study, reverse transcription-quantitative polymerase chain reaction analysis revealed that the expression of MEG3 in MG63 cells was lower compared with in hFOB1.19 cells. Furthermore, it was observed that overexpressing MEG3 in MG63 cells resulted in a decline in the proliferation and invasion, and a marked increase in apoptosis. Additionally, western blotting was used to detect the changes in expression of p53 and MDM2 proto-oncogene, which may be regulated by MEG3, and proteins that associated with cell proliferation, invasion and apoptosis. It was demonstrated that the upregulation of MEG3 significantly increased the transactivation of p53 and induced downstream changes in protein expression. In conclusion, these experiments have demonstrated that MEG3 serves an essential regulatory role in the biological processes of human osteosarcoma cells, and imply that MEG3 may be a marker for predicting the occurrence and development of osteosarcoma.

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Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

MEG3 inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells

Shi

2017

Oncol Lett

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“…MEG3 has been shown to activate p53 by enhancing its stability and transcriptional activity (Zhang et al , 2003; Zhou et al , 2007; Zhou et al , 2012; Zhu et al , 2015). It has been implicated in pituitary tumor and suppresses growth of cancer cells as a tumor suppressor (Zhang et al , 2003; Zhou et al , 2007; Zhou et al , 2012; Zhu et al , 2015). A recent study showed that MEG3 can modulate TGF-β genes by binding to their distal regulatory elements (Mondal et al , 2015).…”

Section: Resultsmentioning

confidence: 99%

Single-cell RNA sequencing reveals an altered gene expression pattern as a result of CRISPR/cas9-mediated deletion of Gene 33/Mig6 and chronic exposure to hexavalent chromium in human lung epithelial cells

Park

Zhang

Yin

et al. 2017

Toxicology and Applied Pharmacology

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Gene 33 (Mig6, ERRFI1) is an adaptor protein with multiple cellular functions. We recently reported that depletion of this protein promotes lung epithelial cell transformation induced by hexavalent chromium [Cr(VI)]. However, the early molecular events that mediate this process are not clear. In the present study, we used single-cell RNA sequencing to compare gene expression profiles between BEAS-2B lung epithelial cells chronically exposed to a sublethal dose of Cr(VI) with or without CRISPR/cas9-mediated deletion of Gene 33. Our data reveal 83 differentially expressed genes. The most notable changes are genes associated with cell adhesion, oxidative stresses, protein ubiquitination, epithelial-mesenchymal transition/metastasis, and WNT signaling. Up-regulation of some neuro-specific genes is also evident, particularly ubiquitin carboxyl-terminal hydrolase L1 (UC HL1), a deubiquitinase and potential biomarker for lung cancer. Gene 33 deletion and/or Cr(VI) exposure did not cause discernable changes in cell morphology. However, Gene 33 deletion led to a modest but significant reduction of cells in the G2/M phase of the cell cycle regardless of Cr(VI) exposure. Gene 33 deletion also significantly reduced cell proliferation. Interestingly, Cr(VI) exposure eliminated the difference in cell proliferation between the two genotypes. Gene 33 deletion also significantly elevated cell migration. Our data indicate that combined Gene 33 deletion and chronic Cr(VI) exposure produces a gene expression pattern and a phenotype resemble those of the transformed lung epithelial cells. Given the known association of UCHL1 with lung cancer, we propose that UCHL1 is an important player in the early stage of lung epithelial cell transformation and tumorigenesis.

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“…A number of studies have demonstrated that lncRNA MEG3, a tumor suppressor gene, was down-regulated in various cancers and was associated with poor prognosis (14)(15)(16)(17)(18). A previous study indicated that the expression of lncRN A MEG3 was clearly lower in osteosarcoma tissues compared with adjacent non-tumor tissues (19).…”

Section: Introductionmentioning

confidence: 99%

“…Zhu et al suggested that MEG3 functions as a tumor suppressor in hepatoma cells through interacting with p53 protein (18). In addition to these studies, the role of MEG3 has been investigated in gallbladder cancer, NSCLC, neuroendocrine tumor, gastric cancer, thyroid carcinoma and so on (25,(14)(15)(16)(17).…”

mentioning

confidence: 99%

MEG3 long non-coding RNA prevents cell growth and metastasis of osteosarcoma

Zhang¹,

Cai²,

Li³

2018

BLL

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OBJECTIVE: This study aimed to investigate the role of long non-coding RNA MEG3 (lncRNA MEG3) in osteosarcoma (OS) and further explore the underlying molecular mechanism. MATERIALS AND METHODS: The expression profi les of MEG3 in OS cell lines and normal osteoblast cell line were detected by qRT-PCR. MEG3 was over-expressed in OS cell line by using LV-MEG3. MTT and colonyformation assays were applied for cell proliferation analysis. Cell migration assay was applied to investigate the cell migration ability. In addition, the expression levels of cell growth and metastasis related factors (Notch1, Hes1, TGF-β, N-cadheren and E-cadheren) were determined to illustrate the mechanisms. RESULTS: We found that compared with normal osteoblast hFOB1.19 cell line, MEG3 was signifi cantly downregulated in MG63 and U2OS cell lines, particularly in MG-63 cells. MEG3 was signifi cantly up-regulated in MG63 cells by LV-MEG3. Cell proliferation and migration ability were obviously repressed by MEG3 over-expression. In addition, MEG3 over-expression markedly inhibited Notch1, Hes1,TGF-β and N-cadheren expression, and the expression level of E-cadheren was improved. CONCLUSIONS: These results indicated that MEG3 could prevent cell growth and metastasis of OS by repressing Notch and TGF-β signaling pathway, thus providing a potential therapeutic target for OS treatment (Tab. 1, Fig. 4, Ref. 30). Text in PDF www.elis.sk.

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Long Noncoding RNA MEG3 Interacts with p53 Protein and Regulates Partial p53 Target Genes in Hepatoma Cells

Cited by 138 publications

References 41 publications

MEG3 inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells

MEG3 inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells

Single-cell RNA sequencing reveals an altered gene expression pattern as a result of CRISPR/cas9-mediated deletion of Gene 33/Mig6 and chronic exposure to hexavalent chromium in human lung epithelial cells

MEG3 long non-coding RNA prevents cell growth and metastasis of osteosarcoma

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