Knockdown of pyruvate kinase type M2 suppresses tumor survival and invasion in osteosarcoma cells both in vitro and in vivo

Yuan, Quan; Yu, Honghao; Chen, Jianhua; Song, Xiaoyu; Sun, Li

doi:10.1016/j.yexcr.2017.11.020

Cited by 17 publications

(22 citation statements)

References 27 publications

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“…Yuan et al reported that PKM2 , which is a rate-limiting enzyme of the glycolytic process, promotes tumor survival in OS cells both in vitro and in vivo. 22 In addition, lactate dehydrogenase A ( LDHA ) is a glycolytic enzyme in the final step of anaerobic glycolysis and was reported to play a crucial role in promoting OS tumor metastasis. 23 Furthermore, aldolase A ( ALDOA ) which catalyzes the conversion of fructose-1,6-bisphosphate was demonstrated to be involved in the development of OS chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

miR-1297 Suppresses Osteosarcoma Proliferation and Aerobic Glycolysis by Regulating PFKFB2

Pan

Tan

et al. 2020

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Background MiR-1297 is reported to function as a tumor suppressor of various cancers. However, the role of miR-1297 in the development of osteosarcoma (OS) has not been elaborated. The purpose of this study was to investigate the functional effects of miR-1297 on OS progression and the underlying mechanism. Methods The expression of protein and mRNA in OS cells was evaluated by Western blotting and quantitative real-time polymerase chain reaction. Cellular proliferation was investigated by cell counting kit-8, colony formation and apoptosis assays. Bioinformatics methods were used to predict target genes. The relationship between PFKFB2 and miR-1297 was demonstrated by dual-luciferase reporter assay. Metabolic changes in OS cells were monitored using an XF96 metabolic flux analyzer. Results We found that miR-1297 was downregulated in OS and that lower expression of miR-1297 promoted proliferation and contributed to the Warburg effect in OS cells. Furthermore, we showed that silencing PFKFB2 inhibited proliferation and reduced aerobic glycolysis while overexpression of PFKFB2 reduced the anti-tumor function of miR-1297 in OS cells. Mechanistically, miR-1297 acted as a tumor suppressor in OS and reduced the expression of PFKFB2 by directly targeting its 3ʹUTR. Conclusion The miR-1297 / PFKFB2 axis regulated OS proliferation by controlling the Warburg effect. Our results revealed a previously undiscovered function of miR-1297 in OS, which strongly linked metabolic alterations with cancer progression. Targeting miR-1297 may become a promising therapeutic approach for OS.

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Section: Discussionmentioning

confidence: 99%

miR-1297 Suppresses Osteosarcoma Proliferation and Aerobic Glycolysis by Regulating PFKFB2

Pan

Tan

et al. 2020

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“…11 Uncontrolled growth, invasion, and metastasis are the main characteristics of tumor cells. 23 A variety of molecules are involved in these processes. For instance, PCNA, a key protein of DNA replication in eukaryotes, is upregulated and reported as a useful biomarker for poor outcome in patients with osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

“…Cell migration was determined by a wound healing method. 23 Briefly, cells seeded into six-well plates were transfected for 24 h, followed by treatment with mitomycin C (1 μg/mL) for 1 h. Then, the medium was replaced with serum-free medium, and a sterile 200-μL pipette tip was used to create a scratch at the bottom of the plate, after which cell debris was washed away and serum-free medium was added. The scratch was photographed at 0 and 24 h using an inverted phase-contrast microscope (Olympus, Tokyo, Japan) at 100 × magnification.…”

Section: Assessment Of Cell Migrationmentioning

confidence: 99%

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Antitumor Effect of miR-1294/Pyruvate Kinase M2 Signaling Cascade in Osteosarcoma Cells

Yuan¹,

Yu²,

Chen³

et al. 2020

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Background: MicroRNAs (miRNAs) can act as negative regulators of gene expression, and play a crucial role in cancer progression. The aim of this study was to investigate the role of miR-1294/pyruvate kinase M2 (PKM2) axis in osteosarcoma cells in vitro and in vivo. Methods: The function of miR-1294 and its association with PKM2 in osteosarcoma cells were studied by real-time PCR, CCK-8, Western blot, scratch test, transwell assay, flow cytometry, and dual-luciferase reporter assays. The effect of miR-1294 on tumor growth in vivo was evaluated in a subcutaneous xenograft model of osteosarcoma. Results: miR-1294 was downregulated in osteosarcoma cells. Forced overexpression of miR-1294 inhibited cell proliferation, migration, and invasion, and induced G0/G1 arrest and apoptosis. Consistently, protein expression levels of proliferating cell nuclear antigen, c-Myc, cyclin D1, active matrix metalloproteinase 2, and active matrix metalloproteinase 9 were decreased, and cleaved caspase 3 and cleaved PARP were increased following miR-1294 overexpression. Moreover, we demonstrated that PKM2 was a target of miR-1294 in osteosarcoma cells, and the effects caused by miR-1294 mimic were reversed by the overexpression of PKM2. Furthermore, we found that upregulation of miR-1294 inhibited tumorigenesis of osteosarcoma cells in vivo, which was accompanied by downregulation of PKM2. Conclusion: Our results revealed that miR-1294/PKM2 signaling cascade exerts important roles in the regulation of tumor progression, implying that this pathway may serve as a potential therapeutic target in osteosarcoma.

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“…Given its promiscuous nature, it is unsurprising that there are a wide range of putative pathways and proteins that have already been implicated in the regulation of autophagy by artemisinin. In our previous studies, a series of molecular targets of ART were successfully identified, with several such as pyruvate kinase M2 (PKM2), heat shock protein 70 (HSP70), heat shock protein family A member 8 (HSPA8), and peroxiredoxin 1 (PRDX1) involved in the regulation of autophagy. Here, we highlight several novel targets and pathways from recent studies.…”

Section: Signaling Pathways and Cellular Targets Involved In Autophagmentioning

confidence: 99%

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

Sun

Yan

Zou

et al. 2019

Medicinal Research Reviews

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Artemisinin and its derivatives, with their outstanding clinical efficacy and safety, represent the most effective and impactful antimalarial drugs. Apart from its antimalarial effect, artemisinin has also been shown to exhibit selective anticancer properties against multiple cancer types both in vitro and in vivo. Specifically, our previous studies highlighted the therapeutic effects of artemisinin on autophagy regulation. Autophagy is a well‐conserved degradative process that recycles cytoplasmic contents and organelles in lysosomes to maintain cellular homeostasis. The deregulation of autophagy is often observed in cancer cells, where it contributes to tumor adaptation to nutrient‐deficient tumor microenvironments. This review discusses recent advances in the anticancer properties of artemisinin and its derivatives via their regulation of autophagy, mitophagy, and ferritinophagy. In particular, we will discuss the mechanisms of artemisinin activation in cancer and novel findings regarding the role of artemisinin in regulating autophagy, which involves changes in multiple signaling pathways. More importantly, with increasing failure rates and the high cost of the development of novel anticancer drugs, the strategy of repurposing traditional therapeutic Chinese medicinal agents such as artemisinin to treat cancer provides a more attractive alternative. We believe that the topics covered here will be important in demonstrating the potential of artemisinin and its derivatives as safe and potent anticancer agents.

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Knockdown of pyruvate kinase type M2 suppresses tumor survival and invasion in osteosarcoma cells both in vitro and in vivo

Cited by 17 publications

References 27 publications

<p>miR-1297 Suppresses Osteosarcoma Proliferation and Aerobic Glycolysis by Regulating PFKFB2</p>

<p>miR-1297 Suppresses Osteosarcoma Proliferation and Aerobic Glycolysis by Regulating PFKFB2</p>

<p>Antitumor Effect of miR-1294/Pyruvate Kinase M2 Signaling Cascade in Osteosarcoma Cells</p>

Targeting autophagy enhances the anticancer effect of artemisinin and its derivatives

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