miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells

Zhao, Shen; Liu, Huailei; Liu, Yaohua; Wu, Jianing; Wang, Chunlei; Hou, Xu; Chen, Xiaofeng; Yang, Guang; Zhao, Ling; Che, Hui; Bi, Yunke; Wang, Hongyu; Peng, Fei; Ai, Jing

doi:10.1016/j.canlet.2013.01.039

Cited by 72 publications

(56 citation statements)

References 42 publications

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“…miR-143, a tumor suppressor miRNA, which is downregulated in many tumors, 66 targets HK-II mRNA. [67][68][69][70][71][72] miR-143 is also expressed in the heart where forced expression decreases the expression of HK-II. 73 Conversely, oncogenic miR-155 upregulates HK-II gene expression in tumor cells by downregulation of miR-143 as well as upregulating HK-II transcription.…”

Section: Hexokinase II In Metabolismmentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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Accumulating evidence reveals that metabolic and cell survival pathways are closely related, sharing common signaling molecules. Hexokinase catalyzes the phosphorylation of glucose, the rate-limiting first step of glycolysis. Hexokinase II (HK-II) is a predominant isoform in insulin-sensitive tissues such as heart, skeletal muscle, and adipose tissues. It is also upregulated in many types of tumors associated with enhanced aerobic glycolysis in tumor cells, the Warburg effect. In addition to the fundamental role in glycolysis, HK-II is increasingly recognized as a component of a survival signaling nexus. This review summarizes recent advances in understanding the protective role of HK-II, controlling cellular growth, preventing mitochondrial death pathway and enhancing autophagy, with a particular focus on the interaction between HK-II and Akt/mTOR pathway to integrate metabolic status with the control of cell survival.

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Section: Hexokinase II In Metabolismmentioning

confidence: 99%

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

2014

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“…Glucose metabolism in glioma is mainly regulated by glycolytic enzymes upregulated under low glucose metabolism stress5203536. HK2 is the first key enzyme for glycolysis and is abundantly expressed in gliomas, moreover, HK2's expression level is negatively correlated with glioma (WHO grade IV) patients' prognosis5.…”

Section: Discussionmentioning

confidence: 99%

PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation

Hou

Liu

et al. 2015

Sci Rep

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Glioma relies on glycolysis to obtain energy and sustain its survival under low glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis regulation are still unclear. Signaling mediated by Double-stranded RNA-activated protein kinase (PKR) – like ER kinase (PERK) is one of the important pathways of unfolded protein response (UPR) which is comprehensively activated in cancer cells upon the hypoxic and low glucose stress. Here we show that PERK is significantly activated in human glioma tissues. PERK silencing results in decreased glioma cell viability and ATP/lactate production upon low glucose stress, which is mediated by partially blocked AKT activation and subsequent inhibition of Hexokinase II (HK2)'s mitochondria translocation. More importantly, PERK silenced glioma cells show decreased tumor formation capacity. Our results reveal that PERK activation is involved in glioma glycolysis regulation and may be a potential molecular target for glioma treatment.

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“…MiR-143 and -195 were identified to regulated the largest number of pathways in MPRN activited by CBP inhibition, including cell cycle (hsa04110) and p53 signaling pathway(hsa04115). Since miR-143 and -195 have tumor-suppressor roles in human glioma [44], [45], we inferred that their reduced expression could impair the potential therapeutic effects of CBP inhibition in glioma. Additionally, in MPRN activated by −STAT3, pathways in cancer (hsa05200) were found to be regulated by the largest number of deregulated miRNAs, with effects on angiogenesis, apoptosis evasion, and proliferation.…”

Section: Resultsmentioning

confidence: 99%

Identification of a Core miRNA-Pathway Regulatory Network in Glioma by Therapeutically Targeting miR-181d, miR-21, miR-23b, β-Catenin, CBP, and STAT3

Ning

et al. 2014

PLoS ONE

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The application of microRNAs (miRNAs) in the therapeutics of glioma and other human diseases is an area of intense interest. However, it’s still a great challenge to interpret the functional consequences of using miRNAs in glioma therapy. Here, we examined paired deep sequencing expression profiles of miRNAs and mRNAs from human glioma cell lines after manipulating the levels of miRNAs miR-181d, -21, and -23b, as well as transcriptional regulators β-catenin, CBP, and STAT3. An integrated approach was used to identify functional miRNA-pathway regulatory networks (MPRNs) responding to each manipulation. MiRNAs were identified to regulate glioma related biological pathways collaboratively after manipulating the level of either post-transcriptional or transcriptional regulators, and functional synergy and crosstalk was observed between different MPRNs. MPRNs responsive to multiple interventions were found to occupy central positions in the comprehensive MPRN (cMPRN) generated by integrating all the six MPRNs. Finally, we identified a core module comprising 14 miRNAs and five pathways that could predict the survival of glioma patients and represent potential targets for glioma therapy. Our results provided novel insight into miRNA regulatory mechanisms implicated in therapeutic interventions and could offer more inspiration to miRNA-based glioma therapy.

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miR-143 inhibits glycolysis and depletes stemness of glioblastoma stem-like cells

Cited by 72 publications

References 42 publications

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

Hexokinase II integrates energy metabolism and cellular protection: Akting on mitochondria and TORCing to autophagy

PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation

Identification of a Core miRNA-Pathway Regulatory Network in Glioma by Therapeutically Targeting miR-181d, miR-21, miR-23b, β-Catenin, CBP, and STAT3

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