MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway

Yu, Tao; Zhao, Yingjun; Hu, Zhixiang; Li, Jing; Chu, Dandan; Zhang, Jiwei; Li, Zhe; Chen, Bing; Zhang, Xiao; Pan, Hongyu; Li, Shengli; Lin, Hechun; Liu, Lei; Yan, Mingxia; He, Xianghuo; Yao, Ming

doi:10.1158/0008-5472.can-17-0671

Cited by 145 publications

(119 citation statements)

References 42 publications

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“…Overall, the reduction in both metabolites and proteins important for glucose metabolism is striking. Reduced levels of HK2, PGAM1, and PGK1 were detected after APIM-peptide treatment, all of which are glycolytic proteins regulated by, or regulating the PI3K/AKT/mTOR pathway and shown to be important for tumor growth and metastasis (Gao & Han, 2018;Liu et al, 2018;Yu et al, 2017). The AMPK pathway is normally activated by a lowered ATP/AMP ratio and serve to increase glucose uptake in order to maintain cellular ATP levels (Faubert, Vincent, Poffenberger, & Jones, 2015).…”

Section: Discussionmentioning

confidence: 99%

PCNA has specific functions in regulation of metabolism in haematological cells

Røst

Olaisen

Sharma³

et al. 2020

Preprint

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PCNA's essential roles in DNA replication and repair are well established, while its recently discovered cytosolic roles are less explored. Here we show that impairing PCNA's cytosolic scaffold functions led to massive changes in cellular signaling, and most strikingly, a strong reduction in glycolytic metabolite and nucleoside phosphate pools in haematological cancer cells. This was not detected in cells from solid tissues nor in primary monocytes from healthy donors. However, lipopolysaccharide stimulated monocytes responded to targeting PCNA's scaffold function similarly to haematological cancer cells, suggesting that cellular stress is an important factor for the observed response. Integrated transcriptome, proteome and metabolome analysis revealed that pathways involved in protein stability/folding and immune responses were affected in haematopoietic cancer cells. Altogether, our data suggests that PCNA has an important role in regulation of cytoplasmic stress via regulation of central carbon metabolism in haematological cells, which potentially can be targeted in cancer treatment.

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Section: Discussionmentioning

confidence: 99%

PCNA has specific functions in regulation of metabolism in haematological cells

Røst

Olaisen

Sharma³

et al. 2020

Preprint

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“…LncRNA MEG3 is reported to regulate cisplatin resistance of NSCLC . MetaLnc9 promotes NSCLC metastasis via activation of AKT/mTOR pathway . LncRNA VELUCT regulates NSCLC cell viability .…”

Section: Introductionmentioning

confidence: 99%

A positive feedback loop between ZNF205‐AS1 and EGR4 promotes non‐small cell lung cancer growth

Lin

Yang

et al. 2018

J Cellular Molecular Medi

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Accumulating evidences revealed that long noncoding RNAs (lncRNAs) are frequently implicated in non‐small cell lung cancer (NSCLC). Herein, we reported the identification of a novel NSCLC‐associated functional lncRNA ZNF205 antisense RNA 1 (ZNF205‐AS1). ZNF205‐AS1 was increased in NSCLC tissues and cell lines, and associated with poor prognosis of NSCLC patients. Bioinformatics prediction, combined with experimental verification revealed that early growth response 4 (EGR4) directly bound to ZNF205‐AS1 promoter, increased the promoter activity of ZNF205‐AS1, and activated ZNF205‐AS1 transcription. Intriguingly, ZNF205‐AS1 transcript directly interacted with EGR4 mRNA, increased EGR4 mRNA stability, and up‐regulated EGR4 expression via RNA‐RNA interaction. Thus, ZNF205‐AS1 and EGR4 formed a positive feedback loop. Through regulating EGR4, ZNF205‐AS1 activated its own promoter activity. EGR4 was also increased in NSCLC and the expression of ZNF205‐AS1 was significantly positively correlated with EGR4 in NSCLC tissues. Gain‐of‐function and loss‐of‐function assays demonstrated that both ZNF205‐AS1 and EGR4 promoted NSCLC cell growth in vitro and NSCLC tumour growth in vivo. Concurrently depleting ZNF205‐AS1 and EGR4 more significantly repressed NSCLC tumour growth in vivo. Collectively, our study demonstrated that the positive feedback loop between ZNF205‐AS1 and EGR4 promotes NSCLC growth, and implied that targeting this feedback loop may be promising therapeutic strategy for NSCLC.

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“…MetaLnc9, as a metastasis‐related LncRNA, was identified to be obviously up‐regulated in highly metastatic cells and NSCLC tumour tissues, and its expression correlated with distant metastasis and TNM. Yu et al indicated that MetaLnc9 could interact with the glycolytic kinase PGK1 and prevent its ubiquitination in NSCLC cells, resulting in activation of the oncogenic AKT/mTOR signalling pathway …”

Section: Main Molecular Mechanism Of Lncrna To Regulate the Metastasimentioning

confidence: 99%

“…Yu et al indicated that MetaLnc9 could interact with the glycolytic kinase PGK1 and prevent its ubiquitination in NSCLC cells, resulting in activation of the oncogenic AKT/mTOR signalling pathway. 95 NF-κB interacting LncRNA (NKILA), encoded by a gene at chromosome 20q13 just near by the prostate transmembrane protein androgen induced 1 (PMEPA1), 96 was increased by NF-κB in breast cancer. 97 Recently, Lu et al discovered that NKILA expression was negatively associated with tumour metastasis in patients with NSCLC, and the expression of NKILA was regulated through classical TGF-β signal pathway, which subsequently inhibited migration and invasion of NSCLC cells through interfering NF-κB/Snail signal pathway in NSCLC cells.…”

Section: Wnt/β-catenin Signal Pathwaymentioning

confidence: 99%

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

Fang

Wang

Gong

et al. 2020

J Cellular Molecular Medi

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Non–small‐cell lung cancer (NSCLC) has become the most lethal human cancer because of the high rate of metastasis. Hence, clarifying the molecular mechanism underlying NSCLC metastasis is very important to improve the prognosis of patients with NSCLC. Long non‐coding RNAs (LncRNAs) are a class of RNA molecules longer than 200 nucleotides, which can participate in diverse biological processes. About 18% of human LncRNAs were recently found to be associated with tumours. Many studies indicated that aberrant expression of LncRNAs played key roles in the progression and metastasis of NSCLC. According to the function in tumours, LncRNAs can be divided into two classes: oncogenic LncRNAs and tumour‐suppressor LncRNAs. In this review, we summarized the main molecular mechanism of LncRNAs regulating NSCLC metastasis, including three aspects: (a) LncRNAs interact with miRNAs as ceRNAs; (b) LncRNAs bind with target proteins; and (c) LncRNAs participate in the transduction of different signal pathways. Then, LncRNAs can exert their function to regulate the metastasis of NSCLC through influencing the progression of epithelial‐mesenchymal transition (EMT) and the properties of cancer stem cell (CSC). But, it is necessary to do some further research to demonstrate the LncRNAs particular regulatory mechanism of inhibiting the metastasis of NSCLC and explore new drugs targeting LncRNAs.

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MetaLnc9 Facilitates Lung Cancer Metastasis via a PGK1-Activated AKT/mTOR Pathway

Cited by 145 publications

References 42 publications

PCNA has specific functions in regulation of metabolism in haematological cells

PCNA has specific functions in regulation of metabolism in haematological cells

A positive feedback loop between ZNF205‐AS1 and EGR4 promotes non‐small cell lung cancer growth

Long non‐coding RNAs: How to regulate the metastasis of non–small‐cell lung cancer

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