Skip to main content
Top
Published in: Tumor Biology 2/2014

01-02-2014 | Research Article

Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer

Authors: Ming Sun, Rui Xia, Feiyan Jin, Tongpeng Xu, Zhijun Liu, Wei De, Xianghua Liu

Published in: Tumor Biology | Issue 2/2014

Login to get access

Abstract

Long noncoding RNAs (lncRNAs) have emerged recently as major players in governing fundamental biological processes, and many of which are altered in expression and likely to have a functional role in tumorigenesis. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a lncRNA associated with various human cancers. However, its biological role and clinical significance in gastric cancer development and progression are unknown. In this study, to investigate the lncRNA MEG3 expression in gastric cancer, quantitative reverse-transcription polymerase chain reaction was conducted. We found that MEG3 levels were markedly decreased in gastric cancer tissues compared with adjacent normal tissues. Its expression level was significantly correlated with TNM stages, depth of invasion, and tumor size. Moreover, patients with low levels of MEG3 expression had a relatively poor prognosis. Furthermore, knockdown of MEG3 expression by siRNA could promote cell proliferation, while ectopic expression of MEG3 inhibited cell proliferation, promoted cell apoptosis, and modulated p53 expression in gastric cancer cell lines. By 5-aza-CdR treatment, we also observed that MEG3 expression can be modulated by DNA methylation. Our findings present that MEG3 downexpression can be identified as a poor prognostic biomarker in gastric cancer and regulate cell proliferation and apoptosis in vitro.
Literature
1.
go back to reference Herszenyi L, Tulassay Z. Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 2010;14(4):249–58.PubMed Herszenyi L, Tulassay Z. Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 2010;14(4):249–58.PubMed
3.
go back to reference Vogiatzi P, Vindigni C, Roviello F, Renieri A, Giordano A. Deciphering the underlying genetic and epigenetic events leading to gastric carcinogenesis. J Cell Physiol. 2007;211(2):287–95. doi:10.1002/jcp.20982.PubMedCrossRef Vogiatzi P, Vindigni C, Roviello F, Renieri A, Giordano A. Deciphering the underlying genetic and epigenetic events leading to gastric carcinogenesis. J Cell Physiol. 2007;211(2):287–95. doi:10.​1002/​jcp.​20982.PubMedCrossRef
4.
go back to reference Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12(3):354–62.PubMed Crew KD, Neugut AI. Epidemiology of gastric cancer. World J Gastroenterol. 2006;12(3):354–62.PubMed
5.
go back to reference Pinheiro H, Bordeira-Carrico R, Seixas S, Carvalho J, Senz J, Oliveira P, et al. Allele-specific CDH1 downregulation and hereditary diffuse gastric cancer. Hum Mol Genet. 2010;19(5):943–52. doi:10.1093/hmg/ddp537.PubMedCrossRef Pinheiro H, Bordeira-Carrico R, Seixas S, Carvalho J, Senz J, Oliveira P, et al. Allele-specific CDH1 downregulation and hereditary diffuse gastric cancer. Hum Mol Genet. 2010;19(5):943–52. doi:10.​1093/​hmg/​ddp537.PubMedCrossRef
6.
go back to reference Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799–816. doi:10.1038/nature05874.PubMedCrossRef Birney E, Stamatoyannopoulos JA, Dutta A, Guigo R, Gingeras TR, Margulies EH, et al. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007;447(7146):799–816. doi:10.​1038/​nature05874.PubMedCrossRef
14.
go back to reference Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G et al. The non-coding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2012. doi:10.1158/0008-5472.CAN-12-2850. Gutschner T, Hammerle M, Eissmann M, Hsu J, Kim Y, Hung G et al. The non-coding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res. 2012. doi:10.​1158/​0008-5472.​CAN-12-2850.
21.
go back to reference Ying L, Huang Y, Chen H, Wang Y, Xia L, Chen Y, et al. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst. 2013;9(3):407–11. doi:10.1039/c2mb25386k.PubMedCrossRef Ying L, Huang Y, Chen H, Wang Y, Xia L, Chen Y, et al. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst. 2013;9(3):407–11. doi:10.​1039/​c2mb25386k.PubMedCrossRef
29.
go back to reference Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39(6):2119–28.PubMedCrossRef Geng YJ, Xie SL, Li Q, Ma J, Wang GY. Large intervening non-coding RNA HOTAIR is associated with hepatocellular carcinoma progression. J Int Med Res. 2011;39(6):2119–28.PubMedCrossRef
31.
go back to reference Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6. doi:10.1158/0008-5472.CAN-11-1021.PubMedCrossRef Kogo R, Shimamura T, Mimori K, Kawahara K, Imoto S, Sudo T, et al. Long noncoding RNA HOTAIR regulates polycomb-dependent chromatin modification and is associated with poor prognosis in colorectal cancers. Cancer Res. 2011;71(20):6320–6. doi:10.​1158/​0008-5472.​CAN-11-1021.PubMedCrossRef
32.
go back to reference Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS, et al. The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 2011;71(11): 3852–62. Khaitan D, Dinger ME, Mazar J, Crawford J, Smith MA, Mattick JS, et al. The melanoma-upregulated long noncoding RNA SPRY4-IT1 modulates apoptosis and invasion. Cancer Res. 2011;71(11): 3852–62.
Metadata
Title
Downregulated long noncoding RNA MEG3 is associated with poor prognosis and promotes cell proliferation in gastric cancer
Authors
Ming Sun
Rui Xia
Feiyan Jin
Tongpeng Xu
Zhijun Liu
Wei De
Xianghua Liu
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1142-z

Other articles of this Issue 2/2014

Tumor Biology 2/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine