Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting β-catenin by activating PKM2 and inactivating PTEN

Zheng, Qidi; Lin, Zhuojia; Xu, Jie; Lu, Yanan; Meng, Qiuyu; Wang, Chen; Yang, Yuxin; Xin, Xiaoru; Li, Xiaonan; Hu, Pu; Gui, Xin; Li, Tianming; Xiong, Wei; Lu, Dongdong

doi:10.1038/s41419-018-0305-7

Cited by 96 publications

(88 citation statements)

References 68 publications

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“…Previous analysis of IPF epithelial cells demonstrated activation of several signaling pathways, including YAP, TGF-β, mTOR/Pi3K/AKT, and WNT/polarity (5,11). MEG3 increases TGF-β signaling by increasing TGF-β target gene expression through recruitment of EZH2 (14,61) and activates mTOR/Pi3K/ AKT through inhibition of PTEN and β-catenin in cancer (13,15). We demonstrated that MEG3 increased YAP1 and AXL mRNAs in H441 and BEAS2B pulmonary adenocarcinoma cells, consistent with our recent findings that YAP signaling is increased in IPF epithelial cells (11).…”

Section: Discussionmentioning

confidence: 99%

“…Pathways regulating differentiation, cell migration, epithelial-mesenchymal transition (EMT), and proliferation, including YAP, TGF-β, mTOR/Pi3K/AKT, and WNT/ planar polarity signaling were activated in IPF epithelial cells (6)(7)(8)(9)(10)(11). Several of these signaling networks are regulated by long noncoding RNAs (LncRNAs), particularly in cancer (12)(13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

Gokey¹,

Snowball²,

Sridharan³

et al. 2018

JCI Insight

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Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease causing fibrotic remodeling of the peripheral lung, leading to respiratory failure. Peripheral pulmonary epithelial cells lose normal alveolar epithelial gene expression patterns and variably express genes associated with diverse conducting airway epithelial cells, including basal cells. Single-cell RNA sequencing of pulmonary epithelial cells isolated from IPF lung tissue demonstrated altered expression of LncRNAs, including increased MEG3. MEG3 RNA was highly expressed in subsets of the atypical IPF epithelial cells and correlated with conducting airway epithelial gene expression patterns. Expression of MEG3 in human pulmonary epithelial cell lines increased basal cell-associated RNAs, including TP63, KRT14, STAT3, and YAP1, and enhanced cell migration, consistent with a role for MEG3 in regulating basal cell identity. MEG3 reduced expression of TP73, SOX2, and Notch-associated RNAs HES1 and HEY1, in primary human bronchial epithelial cells, demonstrating a role for MEG3 in the inhibition of genes influencing basal cell differentiation into club, ciliated, or goblet cells. MEG3 induced basal cell genes and suppressed genes associated with terminal differentiation of airway cells, supporting a role for MEG3 in regulation of basal progenitor cell functions, which may contribute to tissue remodeling in IPF.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

Gokey¹,

Snowball²,

Sridharan³

et al. 2018

JCI Insight

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“…And MEG3 inhibits the growth of HCC cells through the negative regulating PKM2 and β-catenin activity. 36 PI3K-AKT pathway is a major signal cascade regulating glucose metabolism in human cancers. Through activation of PI3K-AKT pathway, Twist, a key regulator of EMT, promotes the glucose metabolism in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Lamc1 promotes the Warburg effect in hepatocellular carcinoma cells by regulating PKM2 expression through AKT pathway

Qin

Wang

et al. 2019

Cancer Biology & Therapy

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Hepatocellular carcinoma (HCC), the most common aggressive malignancy of liver, is the third leading cause of cancer death across the world. Laminin gamma 1 (Lamc1), encodes laminin-γ1, an extracellular matrix protein involved in various progresses such as tumor cell proliferation and metabolism. In the present study, high expression of Lamc1 and PKM2 was observed in tumor tissues of HCC patients. In vitro, down-regulation of Lamc1 inhibited proliferation of HCC cells by promoting cell death, reduced glucose consumption and lactate production, accompanied by a decrease in the expression of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA), and PTEN increased, as well as PTEN S380 and AKT S473/T308 phosphorylation decreased, while Lamc1 up-regulation had the opposite effect. The effects of PKM2 were similar to that of Lamc1 and markedly counteracted the effects of Lamc1 down-regulation. In addition, Lamc1-induced increase in PKM2 expression was strongly attenuated by a PI3K inhibitor, LY294002 or a si-p110 PI3K, with a significant decrease in GLUT1 and LDHA expression, as well as decreased AKT T308 phosphorylation. Thus, we speculated that Lamc1 was implicated in the progression of HCC probably by regulating PKM2 expression through PTEN/AKT pathway.

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“…Herein, MEG3 and p53 were found to induce the expression of each other in BC cells, thus suggesting a potential positive feedback loop between MEG3 and p53. In addition to the p53 pathway, other cancer-related signaling pathways are also modulated by MEG3 in a variety of cancers, such as in the Wnt/β-catenin [34,35], PI3K/AKT [36] and retinoblastoma protein pathways [37]. MicroRNAs involved in tumor cell proliferation and apoptosis are also reported to be modulated by MEG3 [16,17,38].…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of LncRNA MEG3 inhibits cell migration and invasion and enhances cisplatin chemosensitivity in bladder cancer cells

Feng

Zhang

Fan

et al. 2018

neo

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It has been proven that maternally expressed 3 (MEG3), a long non-coding RNA (LncRNA), is down-regulated and inversely correlated with prognosis in various types of cancer, including bladder cancer (BC). Nevertheless, the role of MEG3 in BC has not been fully identified. Herein, we found that MEG3 expression was reduced in 21 BC tumor tissue samples compared to corresponding adjacent tissues. We then established T24 and 5637 cells with a stably integrated expression of MEG3 by G418 resistance screening, and data revealed that the BC cells over-expressing MEG3 displayed weaker migration and invasion ability than control cells. The expression and activity of matrix metalloproteinase (MMP)2 and MMP9 were down-regulated when MEG3 was over-expressed. Moreover, MEG3 over-expression sensitized BC cells to the chemotherapy drug cisplatin (DDP). DDP treatment significantly induced cell apoptosis, down-regulated bcl2 expression, and up-regulated cleaved-caspase-3 and bax expression in BC cells with MEG3 over-expression. MEG3 and p53 can also stimulate mutual expression in BC cells, thus indicating a potential positive feedback loop of MEG3 and p53. Our combined results suggest that over-expression of MEG3 inhibits migration and invasion and enhances DDP chemo-sensitivity in bladder cancer cells.

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Long noncoding RNA MEG3 suppresses liver cancer cells growth through inhibiting β-catenin by activating PKM2 and inactivating PTEN

Cited by 96 publications

References 68 publications

MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

MEG3 is increased in idiopathic pulmonary fibrosis and regulates epithelial cell differentiation

Lamc1 promotes the Warburg effect in hepatocellular carcinoma cells by regulating PKM2 expression through AKT pathway

Up-regulation of LncRNA MEG3 inhibits cell migration and invasion and enhances cisplatin chemosensitivity in bladder cancer cells

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