MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

Background/Aims: Maternally expressed gene 3 (MEG3) is an imprinted gene with maternal expression, which may function as a tumor suppressor by inhibiting angiogenesis. To identify the prognostic value of MEG3 in breast cancer, systematic analysis was performed in this study. Methods: To evaluate gene alteration during breast carcinogenesis, we explored MEG3 expression using the Serial Analysis of Gene Expression Genie suite and Oncomine analysis. The prognostic roles of MEG3 in breast cancer were investigated using the PrognoScan database. The heat map and methylation status of MEG3 were determined using the UCSC Genome Browser. Results: We found that MEG3 was more frequently downregulated in breast cancer than in normal tissues and this correlated with prognosis. However, estrogen receptor and progesterone receptor status were found to be positively correlated with MEG3 expression. Conversely, basal-like status, triple-negative breast cancer status, and Scarff Bloom & Richardson grade criterion were negatively correlated with MEG3 expression. Following data mining in multiple big data databases, we confirmed a positive correlation between MEG3 and heparan sulfate proteoglycan 2 (HSPG2) expression in breast cancer tissues. Conclusion: MEG3 could be adopted as a marker to predict the prognosis of breast cancer with HSPG2. However, large-scale and comprehensive research is needed to clarify our results.

Section: Discussionmentioning

confidence: 99%

Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

Cui¹,

Yi²,

Xuan³

et al. 2018

“…Accumulating data show that MEG3 is overexpressed in normal tissues [24] but downregulated in malignant tumors [10][11][12][13][14][15][16]. Low expression of MEG3 acts as an independent factor for predicting poor prognosis in cancer patients [12,15,25,26], and the downregulation of MEG3 is attributed to its promoter hypermethylation in cancer [27][28][29], and the negative modulation by DNMT1 in glioma [30].…”

Section: Discussionmentioning

confidence: 99%

“…Long non-coding RNAs (lncRNAs), a group of non-coding transcripts that exceed 200 nucleotides in length, is associated with the proliferation, apoptosis and metastasis in a variety of cancers [7][8][9], of which lncRNA maternally expressed gene 3 (MEG3) has been reported to be downregulated in multiple malignancies such as nasopharyngeal carcinoma [10], tongue squamous cell carcinoma (TSCC) [11], hepatocellular carcinoma (HCC) [12], pituitary tumor [13], thyroid carcinoma [14], osteosarcoma [15], and epithelial ovarian carcinoma [16]. Loss of MEG3 or its polymorphisms is associated with clinal stage, distant metastasis, unfavorable survival in patients with thyroid and ovarian carcinomas [14,15], and contributes to cell hypoxia injury [17].…”

Section: Introductionmentioning

confidence: 99%

“…Loss of MEG3 or its polymorphisms is associated with clinal stage, distant metastasis, unfavorable survival in patients with thyroid and ovarian carcinomas [14,15], and contributes to cell hypoxia injury [17]. MEG3 suppresses cell proliferation, cycle progression, invasion [10][11][12][13][14] and induces cell apoptosis [11], leading to the tumorigenesis [16]. These studies suggest that MEG3 may act as a tumor suppressor and a potential biomarker in cancer.…”

Section: Introductionmentioning

confidence: 99%

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lncRNA MEG3 Suppresses the Tumorigenesis of Hemangioma by Sponging miR-494 and Regulating PTEN/ PI3K/AKT Pathway

Dai

Wan

Qiu

et al. 2018

Background/Aims: Dysregulation of long noncoding RNAs (lncRNAs) is associated with the proliferation and metastasis in a variety of cancers, of which lncRNA maternally expressed gene 3 (MEG3) has been indicated as a tumor suppressor in multiple malignancies. However, the underlying mechanisms by which MEG3 contributes to human hemangiomas (HAs) remain undetermined. Methods: qRT-PCR analysis was performed to examine the expression levels of MEG3 and VEGF in proliferating or involuting phase HAs. MTT, colony formation assay, flow cytometry analysis and a subcutaneous xenograft tumor model were conducted to assess the effects of MEG3 on the HAs tumorigenesis. The interaction between MEG3 and miRNAs or their downstream pathways was evidenced by bioinformatic analysis, luciferase report assays, RNA immunoprecipitation (RIP) assay. and Western blot analysis. Results: The expression of MEG3 was substantially decreased and had a negative correlation with VEGF expression in proliferating phase HAs, as compared with the involuting phase HAs and normal skin tissues. Ectopic expression of MEG3 suppressed cell proliferation, colony formation and induced cycle arrest in vitro and in vivo, followed by the downregulation of VEGF and cyclinD1, but knockdown of MEG3 reversed these effects. Furthermore, MEG3 was verified to act as a sponge of miR-494 in HAs cells, and miR-494 counteracted MEG3-caused anti-proliferative effects by regulating PTEN/PI3K/AKT pathway, and exhibited the negative correlation with MEG3 and PTEN expression in proliferating phase HAs. Conclusion: Our findings suggested that lncRNA MEG3 inhibited HAs tumorigenesis by sponging miR-494 and regulating PTEN/PI3K/AKT pathway.

“…In 2013, a report regarded MEG3 as an explicit ceRNA in brain tumor [24]. Except of its competing role in brain tumor, MEG3 could also be an important ceRNA in other cancers and disorders [25,26]. Previous studies have demonstrated that miR-181a as a member of the miR-181family, which exerts as a tumor-promotor gene, is upregulated in many tumors, including chondrosarcoma and gastric cancer [27,28].…”

Section: Introductionmentioning

confidence: 99%

Long Non-Coding RNA MEG3 Functions as a Competing Endogenous RNA to Regulate HOXA11 Expression by Sponging miR-181a in Multiple Myeloma

Shen

Bai

Zhu

et al. 2018

Background/Aims: Long non-coding RNA maternally expressed gene 3 (MEG3) has been reported to play an essential role in cancer progression and metastasis. However, the overall biological role and regulatory mechanism of MEG3 in multiple myeloma (MM) development and progression remains largely ill-defined. Methods: MEG3 and miR-181a expression of MM patients were analyzed by publicly available MM data sets. Cell counting kit-8 and flow cytometry analysis were used to identify the function of MEG3 on MM in vitro. Additionally, we conducted tumor formation experiments in mice models to explain the role of MEG3 on MM in vivo. Then, several mechanism experiments, including dual-luciferase reporter assay and RNA immunoprecipitation were performed to evaluate the emulative relationship between MEG3 and miR-181a. Results: In this research, we found that MEG3 was downregulated in MM patients, which was linked with tumor progression. In addition, we demonstrated that miR-181a was overexpressed in MM patients in consistent with its cancer-promoting function. Importantly, several mechanism experiments revealed that MEG3, acting as an endogenous competitive RNA, could contend with miR-181a to inhibit tumor progression. Furthermore, as the target mRNA of miR-181a, homeobox gene A11(HOXA11) could be positively regulated by MEG3 through sponging miR-181a competitively in vitro. Conclusion: Our present work supplies the first discovery of a MEG3/miR-181a/HOXA11 regulatory network in MM and highlights that MEG3 may serve as a promising target for MM therapy in the future.