Overexpression of pyruvate kinase M2 predicts a poor prognosis for patients with osteosarcoma

Liu, Zheng-xuan; Liang, Hong; Song-qing, Fang; Tan, Guangming; Huang, Pei-guan; Zeng, Zhi; Xue, Xindong; Wang, Xiaoxu

doi:10.1007/s13277-016-5401-7

Cited by 16 publications

(13 citation statements)

References 23 publications

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“…According to the Warburg effect, most cancer cells produce energy by glycolysis, suggesting that targeting cancer metabolism might be a potential field in drug discovery (Liu et al, 2016;Lv et al, 2018;Yang et al, 2017). As a key regulator involving in Warburg effect, PKM2 is frequently expressed at high levels in numerous human tumors and play an important role in tumorigenesis, aerobic glycolysis and chemoresistance (Dayton, Jacks & Vander Heiden, 2016;Guo et al, 2019;Liu et al, 2016;Lv et al, 2018;Zhu et al, 2016). Recent evidents (Chu et al, 2015;Guo et al, 2019;Sun et al, 2015) have indicated that PKM2 is highly over-expressed in LUAC compared to normal lung tissues.…”

Section: Discussionmentioning

confidence: 99%

Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma

Wang

Zhong

Liang

et al. 2020

PeerJ

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Background Pyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis. Methods Firstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using the ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. The Kaplan–Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database. Results Pooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis and also strongly correlated with worse OS (P = 2.80e−14), PPS (P = 0.022), FP (P = 1.30e−6) and RFS (P = 3.41e−8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs). Conclusion This study confirms that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD.

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Section: Discussionmentioning

confidence: 99%

Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma

Wang

Zhong

Liang

et al. 2020

PeerJ

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“…According to the Warburg effect, most cancer cells produce energy by glycolysis, suggesting that targeting cancer metabolism might be a potential field in drug discovery (Liu et al 2016;Lv et al 2018;Yang et al 2017). As a key regulator involving in Warburg effect, PKM2 is frequently expressed at high levels in numerous human tumors, and play an important role in tumorigenesis, aerobic glycolysis and chemoresistance (Dayton et al 2016;Guo et al 2019;Liu et al 2016;Lv et al 2018;Zhu et al 2016). Recent evidents (Chu et al 2015;Guo et al 2019;Sun et al 2015) have indicated that PKM2 is highly over-expressed in LUAC compared to normal lung tissues.…”

Section: Discussionmentioning

confidence: 99%

“…Given that PKM2 is an important driver regulating energy metabolism of cancer cells, targeting PKM2 might be an promising therapeutic strategy. Recent studies have reported that high PKM2 expression is associated with an unfavorable prognosis in multiple human tumors including hepatocellular carcinoma (Lv et al 2018), breast cancer (Yang et al 2017) and osteosarcoma (Liu et al 2016), etc. Nevertheless, over-expression of PKM2 in gastric cancer and pancreatic cancer were not correlated with poor prognosis (Zhu et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Peer Review #2 of "Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma (v0.1)"

2020

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Background. Pyruvate kinase M2 (PKM2) is critical regulator contributing to Warburg effect. However, the expression pattern and prognostic value of PKM2 remain unknown in lung adenocarcinoma (LUAD). The aim of this study is to clarify the prognostic value of PKM2 via intergrated bioinformatics analysis. Methods. Firstly, mRNA expression levels of PKM2 in LUAD were systematically analyzed using ONCOMINE and TCGA databases. Then, the association between PKM2 expression and clinical parameters was investigated by UALCAN. Kaplan-Meier Plotter was used to assess the prognostic significance of PKM2. Finally, the relationship between PKM2 expression and its genetic and epigenetic changes was evaluated with MEXPRESS and MethHC database. Results. Pooled analysis showed that PKM2 is frequently upregulated expression in LUAD. Subsequently, PKM2 expression was identified to be positively associated with tumor stage and lymph node metastasis, and also strongly correlated with worse OS (p=2.80e-14), PPS (p=0.022) , FP (p=1.30e-6) and RFS (p=3.41E-8). Importantly, our results demonstrated that over-expressed PKM2 is associated with PKM2 hypomethylation and copy number variations (CNVs). Conclusion. This study confirmed that over-expressed PKM2 in LUAD is associated with poor prognosis, suggesting that PKM2 might act as a promising prognostic biomarker and novel therapeutic target for LUAD.

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“…It has been reported that PKM2 is increased and its knockdown inhibits survival and invasion of osteosarcoma cells. 17,23 Other miRNAs including miR-133b, 30 miR-214, 31 and miR-139-5p 32 have been implicated in inhibiting cancer cell growth by downregulation of PKM2. Moreover, it is also known that PKM2 contributes to tumor metabolism.…”

Section: Dovepressmentioning

confidence: 99%

“…15,16 Previous research has shown that PKM2 is highly expressed in osteosarcoma and is associated with a poor outcome. 17 However, the association between miR-1294 and PKM2 in osteosarcoma has not been studied. By prediction, we found that PKM2 is a candidate target of miR-1294, indicating that miR-1294/PKM2 pathway may play a role in osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

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

Yuan¹,

Yu²,

Chen³

et al. 2020

OTT

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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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Overexpression of pyruvate kinase M2 predicts a poor prognosis for patients with osteosarcoma

Cited by 16 publications

References 23 publications

Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma

Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma

Peer Review #2 of "Upregulated expression of pyruvate kinase M2 mRNA predicts poor prognosis in lung adenocarcinoma (v0.1)"

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

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