Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression

Peng, Wei-zhao; Si, Shuang; Zhang, Qingxia; Li, Chaofeng; Zhao, Fang; Wang, Fang; Yu, Jia; Ma, Ren

doi:10.1186/s13046-015-0197-7

Cited by 249 publications

(224 citation statements)

References 34 publications

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“…Luo et al claimed that MEG3 can inhibit the proliferation of cancer prostate cells and induce its apoptosis (15). Peng et al maintained that the ectopic expression of MEG3 inhibits proliferation, migration and invasion, and promotes cell apoptosis in gastric cancer (16). These studies show that MEG3 has played a role in the regulation of the proliferation, apoptosis, migration and invasion of cancer cells.…”

Section: Discussionmentioning

confidence: 97%

“…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: 97%

Section: Introductionmentioning

confidence: 99%

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

Shi

2017

Oncol Lett

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“…LncRNA and mRNA co-expression network was built by significantly differently expressed lncRNA and mRNA (36). In addition, some studies also described interactions between lncRNAs and miRNAs (37)(38)(39) or lncRNAs and mRNAs (40) in GC, the results of which showed that lncRNAs may function as a part of GC related regulation network, but lncRNA functions are still poorly explored.…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

Liang

Yao

et al. 2016

International Journal of Oncology

112

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Abstract. Abnormal expression of long non-coding RNAs (lncRNAs) have been shown to play an important role in tumor biology. The Cancer Genome Atlas (TCGA) platform is a large sample sequencing database of lncRNAs, and further analysis of the associations between these data and patients' clinical related information can provide new approaches to find the functions of lncRNA. In the present study, 361 RNA sequencing profiles of gastric cancer (GC) patients were selected from TCGA. Then, we constructed the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network of GC. There were 25 GC specific lncRNAs (fold change >2, p<0.05) identified, 19 of them were included in ceRNA network. Subsequently, we selected these 19 key lncRNAs and analyzed the correlations with clinical features and overall survival, 14 of them were discriminatively expressed with tumor size, tumor grade, TNM stage and lymphatic metastasis (p<0.05). In addition, eight lncRNAs (RPLP0P2, FOXD2-AS1, H19, TINCR, SLC26A4-AS1, SMIM10L2A, SMIM10L2B and SNORD116-4) were found to be significantly associated with overall survival (log-rank p<0.05). Finally, two key lncRNAs HOTAIR and UCA1 were selected for validation of their expression levels in 82 newly diagnosed GC patients by qRT-PCR. Results showed that the fold changes between TCGA and qRT-PCR were 100% in agreement. In addition, we also found that HOTAIR was significantly correlated with tumor size and lymphatic metastasis (p<0.05), and UCA1 was significantly correlated with tumor size, TNM stage and lymphatic metastasis (p<0.05).The clinical relevance of the two lncRNAs and the bioinformatics analysis results were almost the same. Overall, our study showed the GC specific lncRNAs expression patterns and a ceRNA network in GC. Clinical features related to GC specific lncRNAs also suggested these lncRNAs are worthwhile for further study as novel candidate biomarkers for the clinical diagnosis of GC and potential indicators for prognosis. IntroductionNoncoding RNAs (ncRNAs) are transcripts that have no ability of coding proteins, which widely exit in high eukaryotics. According to their characteristics, ncRNAs can be divided into several subtypes including transfer RNA, small nucleolar RNA (snoRNA), ribosomal RNA (rRNA), microRNA (miRNA) and long non-coding RNA (lncRNA). The amount of the ncRNAs transcripts is >98% of the whole genome transcripts and have been suggested to represent transcriptional noise (1). However, more and more evidence indicates that transcriptional output of genome is far more complex than predicted, and suggests new paradigms of ncRNA regulation (2).Recent studies suggest that the ncRNAs may play important biological roles in transcriptional regulation, cellular development, formation of chromosome and RNA modification (3). Based on the transcript size, ncRNAs are grouped into small ncRNAs (<200 bp) and long ncRNAs (>200 bp, up to 100 kb). lncRNA is the functional end-product, and the level of lncRNA expression correlates directly with the level of the active molecule. Thus, ...

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“…MEG3 is decreased in gastric cancer patients and cell lines and downregulation correlates with metastatic disease. Ectopic expression of MEG3 inhibits cell proliferation and migration and promotes apoptosis in several gastric cancer cell lines probably due to sequestration of oncogenic miR-181 (137). Another functional aspect of MEG3 was revealed in several types of cancer cell lines as its capacity to negatively regulate EMT-promoting TGFβ pathway genes (138).…”

Section: Metastasis-related Lncrnas: Category IImentioning

confidence: 99%

“…In CRC cells, GAPLINC promotes cell proliferation and invasion in vitro by binding to PTBassociated splicing factor (PSF) and non-POU-domaincontaining octamer binding protein (NONO), factors which are involved in up-regulation of EMT-promoting factor SNAI-2 (136). For maternally expressed gene 3 (MEG3) lncRNA, sponge-related and RNA-DNA triplex formation based MOA has been described (137,138). MEG3 is decreased in gastric cancer patients and cell lines and downregulation correlates with metastatic disease.…”

Section: Metastasis-related Lncrnas: Category IImentioning

confidence: 99%

Long Non-coding RNAs and their Role in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

171

124

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Abstract.Metastasis is the major cause of death in patients with cancer. It is mediated by a multi-step process referred to as the metastatic cascade (1, 2). Initial steps include local invasion and migration, angiogenesis, epithelialmesenchymal transition (EMT) and intravasation. Tumor cells enter the circulation as single cells or circulating tumor cell clusters, are coated by platelets to escape an immune response and subsequently arrest in capillaries in distant organs as a prerequisite for extravasation. Colonization starts by homing of tumor cells in supporting niches of the organ parenchyma, followed by a latency phase which can last from several months to decades. A prerequiste for overt outgrowth of micrometastases is their adaptation to the local microenvironment and acquisition of colonisation-promoting traits (3-6). The pattern of colonized distant organs depends on the tumor type and can range from predominant spread to one organ and colonization of different types of organs sequentially or simultaneously (7). Several genes and their products have been identified to mediate crucial steps of the metastatic process such as metastasis initiation and progression, as well as organ-specific functions of metastasis (virulence) (8, 9). These gene products include proteases, chemokines, cytokines and their receptors, angiogenic factors, intracellular and transmembrane kinases, adhesion molecules, components of the extracellular matrix (ECM), GPI-linked receptors and carbohydrate metabolism-related enzymes (8, 9). More recently, an important impact of RNA-related molecules for metastasis has emerged. MicroRNAs (miRs) and other types of RNA modulate metastasis via regulatory networks (10,11). In this review we focus on the role of long non-coding RNAs (lncRNA) as promoters or inhibitors of metastasis in different tumor entities since there is an urgent need to define new targets for therapeutic intervention. With the exception of denosumab for treatment of bone metastases, all other agents evaluated in clinical studies for treatment of metastatic disease gave rise to mixed or disappointing results (6).

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Long non-coding RNA MEG3 functions as a competing endogenous RNA to regulate gastric cancer progression

Cited by 249 publications

References 34 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

Integrated analysis of long non-coding RNA competing interactions reveals the potential role in progression of human gastric cancer

Long Non-coding RNAs and their Role in Metastasis

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