The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells

Liu, Lixuan; Deng, Wei; Zhou, Xiao‐Tao; Chen, Rui-Pei; Xiang, Mengqi; Guo, Y.; Pu, Ze‐Jin; Li, Rui; Wang, Gefei; Wu, Ling‐Fei

doi:10.3892/ijo.2015.3248

Cited by 41 publications

(33 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…p53, as a tumour suppressor, inhibits tumours by regulating downstream gene expression (22,23). Some studies showed that MEG3 functions by activating p53 (17,18) while other studies indicated that the activation of p53 may be achieved by means of the inhibition of MEG3 on MDM2 (a major inhibitor of p53) (24)(25)(26). Our study found that p53 and MDM2 are important mediators through which MEG3 inhibits osteosarcoma.…”

Section: Introductionmentioning

confidence: 68%

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

Shi

2017

Oncol Lett

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 68%

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

Shi

2017

Oncol Lett

View full text Add to dashboard Cite

show abstract

“…It has been reported that hypermethylation of the MEG3 regulatory region has also been associated with the loss of MEG3 expression in human tumors cell lines, such as pituitary tumors 27 , gliomas 45 and hepatoma 46 . In the present study, we found that environmental carcinogen nickel resulted in the hypermethylation of MEG3 regulatory region in normal human bronchial epithelial cells, and that treatment of cells with DNA methylation inhibitor 5-aza-2-deoxycytidine (5-Aza) increased in MEG3 expression, strongly indicating that the promoter hypermethylation mediates downregulation of MEG3 transcription due to nickel exposure.…”

Section: Discussionmentioning

confidence: 99%

LncRNA MEG3 downregulation mediated by DNMT3b contributes to nickel malignant transformation of human bronchial epithelial cells via modulating PHLPP1 transcription and HIF-1α translation

et al. 2017

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) are emerging as key players in various fundamental cellular biological processes, and many of them are likely to have functional roles in tumorigenesis. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes an lncRNA, and the decreased MEG3 expression has been reported in multiple cancer tissues. However, nothing is known about the alteration and role of MEG3 in environmental carcinogen-induced lung tumorigenesis. Our present study, for the first time to the best of our knowledge, discovered that environmental carcinogen nickel exposure led to MEG3 downregulation, consequently initiating c-Jun-mediated PHLPP1 transcriptional inhibition and hypoxia-inducible factor-1α (HIF-1α) protein translation upregulation, in turn resulting in malignant transformation of human bronchial epithelial cells. Mechanistically, MEG3 downregulation was attributed to nickel-induced promoter hypermethylation via elevating DNMT3b expression, while PHLPP1 transcriptional inhibition was due to the decreasing interaction of MEG3 with its inhibitory transcription factor c-Jun. Moreover, HIF-1α protein translation was upregulated via activating the Akt/p70S6K/S6 axis resultant from PHLPP1 inhibition in nickel responses. Collectively, we uncover that nickel exposure results in DNMT3b induction and MEG3 promoter hypermethylation and expression inhibition, further reduces its binding to c-Jun and in turn increasing c-Jun inhibition of PHLPP1 transcription, leading to the Akt/p70S6K/S6 axis activation, and HIF-1α protein translation as well as malignant transformation of human bronchial epithelial cells. Our studies provide a significant insight into understanding the alteration and role of MEG3 in nickel-induced lung tumorigenesis.

show abstract

“…Human maternally expressed gene 3 (MEG3) is a maternally expressed imprinted gene that encodes a length of 1.6 kb nucleotides which suggests to function as a non-coding RNA 8 . Recent studies have demonstrated that MEG3 is abnormal expressed in various human cancers, such as retinoblastoma 9 , colorectal cancer 10 , and hepatocellular carcinoma 11 . More important, our previous study has proved that MEG3 was down-regulated and affected cell proliferation and apoptosis in cervical cancer 12 .…”

Section: Introductionmentioning

confidence: 99%

Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer

Zhang

Yao

Lin

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Methylation alterations of specific genes have recently been identified as diagnostic biomarkers for human cancers. Although MEG3 has been proved to be a tumor suppressor in cervical cancer according to our previous study, the diagnostic value of MEG3 methylation in plasma is still unknown. Therefore, the aim of this study is to identify a novel epigenetic biomarker for cervical cancer. In the current study, the level of MEG3 methylation was evaluated using methylation-specific polymerase chain reaction. The results showed that the level of MEG3 methylation was significantly higher in cervical cancer tissues and patients’ plasmas than those in adjacent normal tissues and plasmas of healthy participants respectively. Moreover, the accuracy was good enough for MEG3 methylation in plasma to discriminate CIN III patients from healthy participants. In addition, MEG3 methylation in plasma also has high discriminating power to predict HR-HPV infection and lymph node metastasis. Furthermore, hypermethylation of MEG3 in plasma was associated with worse recurrence-free and overall survival in cervical cancer patients. In conclusions, MEG3 methylation in plasma can serve as a diagnostic and prognostic biomarker for cervical cancer, providing useful information for clinical management.

show abstract

The mechanism of adenosine-mediated activation of lncRNA MEG3 and its antitumor effects in human hepatoma cells

Cited by 41 publications

References 32 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

LncRNA MEG3 downregulation mediated by DNMT3b contributes to nickel malignant transformation of human bronchial epithelial cells via modulating PHLPP1 transcription and HIF-1α translation

Aberrant Methylation of MEG3 Functions as a Potential Plasma-Based Biomarker for Cervical Cancer

Contact Info

Product

Resources

About