MicroRNA-202 suppresses glycolysis of pancreatic cancer by targeting hexokinase 2
© The author(s)..
Purpose: Various studies have identified miR-202 critically participated in the development of different cancers. However, the potential mechanisms underlying the carcinogenesis of pancreatic cancer (PC) still remains elusive. Methods: In the study, cell proliferation assay, colony formation assay, EdU incorporation assay, Luciferase reporter assay, lactate production, glucose consumption assay, real-time PCR and western blot were used to investigate the mechanism of hexokinase 2 (HK2) regulated by miR-202 in pancreatic cancer in vitro and in vivo. Results: Here we found that miR-202 was decreased in the PC tissues, and its low expression was correlated with a poor prognosis of PC patients. Overexpression of miR-202 in PC cells reduced cell proliferation and tumorigenesis by impairing glycolysis, while downregulation of miR-202 promoted the cells proliferative capacity. Mechanically, we demonstrated that HK2, an enzyme that catalyzes the irreversible rate-limiting step of glycolysis, as the direct target of miR-202. Overexpression of miR-202 suppressed both the mRNA and protein levels of HK2, whereas re-introduction of HK2 abrogated miR-202-mediated glycolytic inhibition. In addition, the expression of miR-202 was negatively associated with HK2 level in a cohort of PC tissues. Conclusion: Our findings validate the mechanism that miR-202 reprograms the metabolic process to promote PC progression, thus providing potential prognostic predictors for PC patients.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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Enthalten in: |
Journal of Cancer - 12(2021), 4 vom: 06., Seite 1144-1153 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Wang, Shuang-Jia [VerfasserIn] |
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Links: |
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Themen: |
Glycolysis |
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Anmerkungen: |
Date Revised 15.01.2021 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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doi: |
10.7150/jca.43379 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM320056961 |
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520 | |a Purpose: Various studies have identified miR-202 critically participated in the development of different cancers. However, the potential mechanisms underlying the carcinogenesis of pancreatic cancer (PC) still remains elusive. Methods: In the study, cell proliferation assay, colony formation assay, EdU incorporation assay, Luciferase reporter assay, lactate production, glucose consumption assay, real-time PCR and western blot were used to investigate the mechanism of hexokinase 2 (HK2) regulated by miR-202 in pancreatic cancer in vitro and in vivo. Results: Here we found that miR-202 was decreased in the PC tissues, and its low expression was correlated with a poor prognosis of PC patients. Overexpression of miR-202 in PC cells reduced cell proliferation and tumorigenesis by impairing glycolysis, while downregulation of miR-202 promoted the cells proliferative capacity. Mechanically, we demonstrated that HK2, an enzyme that catalyzes the irreversible rate-limiting step of glycolysis, as the direct target of miR-202. Overexpression of miR-202 suppressed both the mRNA and protein levels of HK2, whereas re-introduction of HK2 abrogated miR-202-mediated glycolytic inhibition. In addition, the expression of miR-202 was negatively associated with HK2 level in a cohort of PC tissues. Conclusion: Our findings validate the mechanism that miR-202 reprograms the metabolic process to promote PC progression, thus providing potential prognostic predictors for PC patients | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Glycolysis | |
650 | 4 | |a Hexokinase 2 | |
650 | 4 | |a Pancreatic cancer | |
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700 | 1 | |a Guo, Ping |e verfasserin |4 aut | |
700 | 1 | |a Feng, Liu-Xing |e verfasserin |4 aut | |
700 | 1 | |a Li, Bin |e verfasserin |4 aut | |
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