PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells

Özcan, Selahattin Can; Sarioglu, Aybike; Altunok, Tugba Hazal; Akkoç, Ahmet; Guzel, Saime; Guler, Sabire; Imbert-Fernandez, Yoannis; Muchut, Robertino J.; Iglesias, Alberto A.; Gurpinar, Yunus; Clem, Amy; Chesney, Jason; Yalçin, Ali

doi:10.1007/s11010-020-03751-5

Cited by 36 publications

(34 citation statements)

References 45 publications

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“…Glycolysis and fatty acid oxidation change from fetal to mature tissue (50). Pfkfb2 has been reported to play a special role in regulating glycolysis and proliferation in pancreatic cancer cells (51). In addition, four (Dhcr24, Nacad, Slc16a3, and Slc7a5) of eight hub genes were found to be decreased in P7 heart tissues.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome of Heart via MeRIP After Birth: Day 0 vs. Day 7

Yang

Zhao

Zhang

et al. 2021

Front. Cardiovasc. Med.

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Aim: To systematically classify the profile of the RNA m6A modification landscape of neonatal heart regeneration.Materials and Methods: Cardiomyocyte proliferation markers were detected via immunostaining. The expression of m6A modification regulators was detected using quantitative real-time PCR (qPCR) and Western blotting. Genome-wide profiling of methylation-modified transcripts was conducted with methylation-modified RNA immunoprecipitation sequencing (m6A-RIP-seq) and RNA sequencing (RNA-seq). The Gene Expression Omnibus database (GEO) dataset was used to verify the hub genes.Results: METTL3 and the level of m6A modification in total RNA was lower in P7 rat hearts than in P0 ones. In all, 1,637 methylation peaks were differentially expressed using m6A-RIP-seq, with 84 upregulated and 1,553 downregulated. Furthermore, conjoint analyses of m6A-RIP-seq, RNA-seq, and GEO data generated eight potential hub genes with differentially expressed hypermethylated or hypomethylated m6A levels.Conclusion: Our data provided novel information on m6A modification changes between Day 0 and Day 7 cardiomyocytes, which identified that increased METTL3 expression may enhance the proliferative capacity of neonatal cardiomyocytes, providing a theoretical basis for future clinical studies on the direct regulation of m6A in the proliferative capacity of cardiomyocytes.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome of Heart via MeRIP After Birth: Day 0 vs. Day 7

Yang

Zhao

Zhang

et al. 2021

Front. Cardiovasc. Med.

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“…The changes in key enzymes can lead to an enhanced glycolytic ability, promote glucose uptake into tumor cells and increase the accumulation of lactic acid, thus further supporting tumor growth and development ( 21 ). 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB2) is an enzyme that regulates the synthesis and degradation of fructose-2,6-bisphosphate (Fru-2, 6-P2), which is widely expressed in a variety of cancer cells, such as ovarian, breast and pancreatic cancer cells ( 22 , 23 ). By regulating the expression of Fru-2, 6-P2 (a signaling metabolite that participates in glycolysis), the PFKFB family has been found to regulate intracellular glycolysis in cancer by acting as an oncogene ( 24 , 25 ).…”

Section: Introductionmentioning

confidence: 99%

Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer

Sha

Liu

et al. 2021

Mol Med Rep

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Lung cancer is one of the most lethal diseases and therefore poses a significant threat to human health. The Warburg effect, which is the observation that cancer cells predominately produce energy through glycolysis, even under aerobic conditions, is a hallmark of cancer. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB) is an important regulator of glycolysis. Shikonin is a Traditional Chinese herbal medicine, which has been reported to exert antitumor effects. The present study aimed to investigate the anticancer activity of shikonin in lung cancer. Cell Counting Kit-8 (CCK-8) and colony formation assays were used to analyze proliferation in A549 and H446 cells. Wound healing and Transwell assays were used to measure migration and invasion in A549 and H446 cells. Cell apoptosis was analyzed using flow cytometry. Lactate levels, glucose uptake and cellular ATP levels were measured using their corresponding commercial kits. Western blotting was performed to analyze the protein expression levels of key enzymes involved in aerobic glucose metabolism. Reverse transcription-quantitative PCR was used to analyze the mRNA expression levels of PFKFB2. The results of the present study revealed that PFKFB2 expression levels were significantly upregulated in NSCLC tissues. Shikonin treatment decreased the proliferation, migration, invasion, glucose uptake, lactate levels, ATP levels and PFKFB2 expression levels and increased apoptosis in lung cancer cells in a dose-dependent manner. The overexpression of PFKFB2 increased the proliferation, migration, glucose uptake, lactate levels and ATP levels in lung cancer cells, while the knockdown of PFKFB2 expression exerted the opposite effects. Moreover, there were no significant differences in lung cancer cell migration, apoptosis, glucose uptake, lactate levels and ATP levels between cells with knocked down PFKFB2 expression or treated with shikonin and the knockdown of PFKFB2 in cells treated with shikonin. In conclusion, the results of the present study revealed that shikonin inhibited the Warburg effect and exerted antitumor activity in lung cancer cells, which was associated with the downregulation of PFKFB2 expression.

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“…A previous study showed LY9 was related to the cancer progression and correlated to overall survival of the patients with breast cancer. PFKFB2 is an enzyme involved in regulating the Warburg effect (also termed as glycolysis) [32]. PFKFB2 had been found to have a key role in regulating tumor growth and survival in multiple cancer types, including gastric cancer, gliomas, and osteosarcoma [32][33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…PFKFB2 is an enzyme involved in regulating the Warburg effect (also termed as glycolysis) [32]. PFKFB2 had been found to have a key role in regulating tumor growth and survival in multiple cancer types, including gastric cancer, gliomas, and osteosarcoma [32][33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma

Wang

Qin²,

Liu

et al. 2020

Computational and Mathematical Methods in Medicine

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Osteosarcoma (OS) is one of the most common types of primary bone tumors in early adolescence with unsatisfied prognosis. Aberrant DNA methylation had been demonstrated to be related to tumorigenesis and progression of multiple cancers and could serve as the potential biomarkers for the prognosis of human cancers. In conclusion, this study identified 18 downregulated hypomethylation genes and 52 upregulated hypomethylation genes in OS by integrating the analysis the GSE97529 and GSE42572 datasets. Bioinformatics analysis revealed that OS-specific methylated genes were involved in regulating multiple biological processes, including chemical synaptic transmission, transcription, response to drug, and regulating immune response. KEGG pathway analysis showed that OS-specific methylated genes were associated with the regulation of Hippo, cAMP calcium, MAPK, and Wnt signaling pathways. By analyzing R2 datasets, this study showed that the dysregulation of these OS-specific methylated genes was associated with the metastasis-free survival time in patients with OS, including CBLN4, ANKMY1, BZW1, KRTCAP3, GZMB, KRTDAP, LY9, PFKFB2, PTPN22, and CLDN7. This study provided a better understanding of the molecular mechanisms underlying the progression and OS and novel biomarkers for the prognosis of OS.

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PFKFB2 regulates glycolysis and proliferation in pancreatic cancer cells

Cited by 36 publications

References 45 publications

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome of Heart via MeRIP After Birth: Day 0 vs. Day 7

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome of Heart via MeRIP After Birth: Day 0 vs. Day 7

Shikonin inhibits the Warburg effect, cell proliferation, invasion and migration by downregulating PFKFB2 expression in lung cancer

Integrated Genome-Wide Methylation and Expression Analyses Reveal Key Regulators in Osteosarcoma

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