Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma
Abstract
:1. Introduction
2. Results
2.1. Identification of PKM2 Expression in RCC
2.2. PKM2 Knockdown Inhibits Tumor Progression of 786-O Cells
2.3. PKM2 Knockdown Induces Autophagy
2.4. PKM2 Knockdown Impairs Glycolysis, Glycolytic Intermediates, and Mitochondrial Activity
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Kidney Tumor and Normal Tissues
4.3. Immunohistochemical Analysis
4.4. Cell Lines and Cell Culture
4.5. PKM2 Knockdown
4.6. Cell Viability Assay
4.7. Western Blot Analysis
4.8. Immunofluorescence Analysis
4.9. Subcellular Fractionation
4.10. Acridine Orange Staining
4.11. Monodansylcadaverine Staining
4.12. Analysis of Glycolysis, Glycolytic Intermediates, and Mitochondrial Activity
4.13. In Vitro Cell Migration and Invasion Assay
4.14. Colony Formation Assay
4.15. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
PKM2 | pyruvate kinase M2 |
RCC | renal cell carcinoma; LDHA |
LDHA | lactate dehydrogenase A |
Glut-1 | pyruvate kinase M2 |
siRNA | small-interfering RNA |
AKT | protein kinase B |
mTOR | mechanistic target of rapamycin 1 |
ccRCC | clear cell renal cell carcinoma |
TK | tyrosine kinase |
ERK 1/2 | extracellular signal-regulated kinase 1/2 |
TMA | tissue microarray |
HPLC | high-performance liquid chromatography |
OCR | oxygen consumption rate |
MMP | matrix metalloproteinase |
PER | proton efflux rate |
glycoPER | glycolytic proton efflux rate |
HIF-1 | hypoxia-inducible factor-1 |
LC3B | light chain 3B |
AMPK | AMP-activated protein kinase |
GSK3β | glycogen synthase kinase 3 beta |
PI3K | phosphoinositide 3-kinase |
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Tumor Stage and Grade | Variable | No. of Samples | Healthy Subject (%) | Cancer Patient (%) | ||
---|---|---|---|---|---|---|
<60 | >60 | <60 | >60 | |||
Patients (Male and Female) | 70 Cancer Patients, 10 Healthy Subjects | 10 (100%) | - | 6 (60%) | 4 (40%) | |
Tumor stage (%) | I | 15 | - | - | 12 (17.14%) | 3 (4.29%) |
II | 29 | - | - | 19 (27.14%) | 10 (14.29%) | |
III | 24 | - | - | 15 (21.43%) | 9 (12.86%) | |
IV | 2 | - | - | - | 2 (2.86%) | |
TNM grade | T1N0M0 | - | - | - | 12 (17.14%) | 3 (4.29%) |
T2N0M0 | - | - | - | 19 (27.14%) | 10 (14.29%) | |
T3N0M0 | - | - | - | 7 (10%) | 4 (5.71%) | |
T3NxM0 | - | - | - | 1 (1.43%) | 1 (1.43%) | |
T3aN0M0 | - | - | - | 5 (7.14%) | 4 (5.71%) | |
T3bN1M0 | - | - | - | 1 (1.43%) | - | |
T3aNxM0 | - | - | - | 1 (1.43%) | - | |
T4N0M0 | - | - | - | - | 1 (1.43%) | |
T4N1M1 | - | - | - | - | 1 (1.43%) |
siRNAs | Sense Stand Sequences | Source |
---|---|---|
si27 | AGGCAGAGGCUGCCAUCUA | Bioneer Corporation |
si155 | GCCAUAAUCGUCCUCACCA | |
si156 | CCAUAAUCGUCCUCACCAA | |
siCT (negative control siRNA targeting the firefly luciferase gene) | CUUACGCUGAGUACUUCGA | |
siPK (positive control siRNA, commercially available, targeting both PKM1 and PKM2 mRNAs) | GGACCUGAGAUCCGAACUG |
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Dey, P.; Son, J.Y.; Kundu, A.; Kim, K.S.; Lee, Y.; Yoon, K.; Yoon, S.; Lee, B.M.; Nam, K.T.; Kim, H.S. Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma. Int. J. Mol. Sci. 2019, 20, 5622. https://doi.org/10.3390/ijms20225622
Dey P, Son JY, Kundu A, Kim KS, Lee Y, Yoon K, Yoon S, Lee BM, Nam KT, Kim HS. Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma. International Journal of Molecular Sciences. 2019; 20(22):5622. https://doi.org/10.3390/ijms20225622
Chicago/Turabian StyleDey, Prasanta, Ji Yeon Son, Amit Kundu, Kyeong Seok Kim, Yura Lee, Kyungsil Yoon, Sungpil Yoon, Byung Mu Lee, Ki Taek Nam, and Hyung Sik Kim. 2019. "Knockdown of Pyruvate Kinase M2 Inhibits Cell Proliferation, Metabolism, and Migration in Renal Cell Carcinoma" International Journal of Molecular Sciences 20, no. 22: 5622. https://doi.org/10.3390/ijms20225622