Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line

Chunharojrith, Paweena; Nakayama, Yuki; Jiang, Xiaobing; Kery, Rachel E.; Ma, Jun; Ulloa, Cristine S. De La Hoz; Zhang, Xun; Zhou, Yunli; Klibanski, Anne

doi:10.1016/j.mce.2015.08.018

Cited by 63 publications

(42 citation statements)

References 57 publications

(85 reference statements)

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“…MEG3 expression has reportedly caused apoptosis in numerous tumor cell lines, including tongue squamous cell carcinoma lines CAL-27 and SCC-15 (32), non-small cell lung cancer lines SPC-A1 and A549 (33), and glioma line U251 (34). Previous data indicated that MEG3 suppresses tumor growth by causing cell cycle G1 arrest (35). Therefore, the underlying mechanism of tumor suppression through MEG3 in GH-secreting pituitary tumors remains to be investigated.…”

Section: Discussionmentioning

confidence: 99%

MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH‑secreting adenomas

et al. 2019

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Overactivation of the Gs-mediated pathway by mutations of the G-protein α subunit (Gsα), a gsp oncogene, results in increased growth hormone (GH) hypersecretion and reduced tumor volume in patients with GH-secreting pituitary tumors. However, the mechanism underlying the clinical characteristics of gsp oncogene requires further investigation. Cyclic adenosine monophosphate-responsive element binding (CREB), as a downstream target gene of gsp oncogene, is implicated in activating maternally expressed gene 3 (MEG3). The present study proposes that gsp oncogene mediates MEG3-regulating GH hypersecretion, resulting in the small tumor size of GH-secreting tumors. Therefore, the present study detected Gsα mutations by polymerase chain reaction in GH-secreting tumors, and revealed that Gsα mutations were observed in 7/25 (28%) GH-secreting tumors. Gsp-positive tumors indicated significantly increased levels of phosphorylated p-CREB (P<0.0001) and MEG3 (P=0.039), compared with gsp-negative tumors. The results indicated that MEG3 levels were positively correlated with GH and IGF-1 levels, and negatively correlated with the tumor volume of GH-secreting tumors. The group with gsp-positive or with high MEG3 expression indicated a significantly reduced proportion of invasiveness and lower Ki-67 index, compared with the gsp-negative or low MEG3 expression group. In conclusion, gsp oncogene may mediate MEG3 by promoting GH hypersecretion, resulting in smaller tumors, as well as suppressing proliferation and invasiveness of GH-secreting pituitary tumors.

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Section: Discussionmentioning

confidence: 99%

MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH‑secreting adenomas

et al. 2019

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“…Re-expression of MEG3 lncRNA is reported to suppress the tumor growth in both in vitro and in vivo animal models [33]. Inactivation of MEG3 lncRNA gene is reported to increase the expression of angiogenesis promoting genes and microvessel formation in the brain [34]. Moreover, in MEG3-knockout mouse quantitative PCR and immuno-histological staining showed increased expression of VEGF pathway genes and increased cortical microvessel density [35].…”

Section: Lncrna and Angiogenesismentioning

confidence: 99%

LncRNA as a Therapeutic Target for Angiogenesis

Kumar

Goyal

2017

CTMC

209

142

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Background: Out of 3 billion base pairs in human genome only ~2% code for proteins; and out of 180,000 transcripts in human cells, about 20,000 code for protein, remaining 160,000 are non-coding transcripts. Most of these transcripts are more than 200 base pairs and constitute a group of long non-coding RNA (lncRNA). Many of the lncRNA have its own promoter, and are well conserved in mammals. Accumulating evidence indicates that lncRNAs act as molecular switches in cellular differentiation, movement, apoptosis, and in the reprogramming of cell states by altering gene expression patterns. However, the role of this important group of molecules in angiogenesis is not well understood. Angiogenesis is a complex process and depends on precise regulation of gene expression. Conclusion:Dysregulation of transcription during this process may lead to several diseases including various cancers. As angiogenesis is an important process in cancer pathogenesis and treatment, lncRNA may be playing an important role in angiogenesis. In support of this, lncRNA microvascular invasion in hepatocellular carcinoma (MVIH) has been shown to activate angiogenesis. Furthermore, lncRNA-Meg3-knockout mouse showed increased expression of vascular endothelial growth factor pathway genes and increased cortical microvessel density. Overall, there is strong evidence that lncRNA is an important class of regulatory molecule, and a number of studies have demonstrated that these can be targeted to change cellular physiology and functions. In this review, we have attempted to summarize these studies and elucidate the potential of this novel regulatory molecule as a therapeutic target.

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“…Maternally expressed gene 3 (MEG3), a long non-coding RNA (lncRNA), has been extensively identified in various normal tissues (11). In various types of tumor, loss of MEG3 expression enhances the progression of tumors; therefore, ectopic expression of MEG3 may suppress cancer cell proliferation (12,13).…”

Section: Introductionmentioning

confidence: 99%

LncRNA MEG3 ameliorates respiratory syncytial virus infection by suppressing TLR4 signaling

et al. 2017

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Maternally expressed gene 3 (MEG3), a long noncoding RNA (lncRNA) has been dysregulated in various tumors. However, the expression level and functional role of MEG3 in the progression of respiratory syncytial virus (RSV) infection remains to be elucidated. The present study quantified the expression level of MEG3 in the nasopharyngeal (NPA) samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. The findings of the present study demonstrated that the expression level of lncRNA MEG3 was reduced in the NPA samples of RSV‑infected patients and in BEAS‑2B cells infected with RSV. In vitro transfection revealed increased mRNA expression levels of toll‑like receptor 4 (TLR4), tumor necrosis factor‑α (TNFα) and interleukin (IL)‑8 following RSV infection in BEAS‑2B cells. Additionally, ectopic expression of MEG3 reduced the expression level of TLR4, subsequently suppressing the mRNA expression levels of TNFα and IL‑8, indicating the protective role of MEG3 in the process of RSV infection. It is of note, that RSV infection‑induced p38 mitogen activated protein kinase (MAPK) and nuclear factor‑κB (NF‑κB) activation was partly abolished by overexpression of MEG3. In conclusion, to the best of our knowledge, the present study provided the first evidence that lncRNA MEG3 expression level was reduced in the NPA samples of patients with RSV infection and RSV‑infected cells. Additionally, it was demonstrated that MEG3 protected human airway epithelial cells from RSV infection, primarily by suppressing TLR4‑dependent p38 MAPK and NF‑κB signaling.

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Tumor suppression by MEG3 lncRNA in a human pituitary tumor derived cell line

Cited by 63 publications

References 57 publications

MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH‑secreting adenomas

MEG3 is associated with gsp oncogene regulation of growth hormone hypersecretion, proliferation and invasiveness of human GH‑secreting adenomas

LncRNA as a Therapeutic Target for Angiogenesis

LncRNA MEG3 ameliorates respiratory syncytial virus infection by suppressing TLR4 signaling

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