Let-7g Upregulation Attenuated the KRAS–PI3K–Rac1–Akt Axis-Mediated Bioenergetic Functions
"> Figure 1
<p>Dysfunction of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) by naringenin (NGN) confers apoptosis in nasopharyngeal carcinoma (NPC) cells. (<b>A</b>) The effect of NGN on NPC and Smulow–Glickman (S-G) cell growth. Cells treated with vehicle (−) or the indicated concentrations of NGN for 36 h. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay determined cell growth. (<b>B</b>–<b>F</b>) The effects of NGN on the induction of NPC cell growth inhibition and apoptosis. After 36 h treatment with (−), NGN (160 μM), Z-VAD-FMK (8 μM) or NGN (160 μM) and Z-VAD-FMK (8 μM), cell growth and viability were determined by the MTT and flow cytometric analysis of PI uptake, respectively. DNA fragmentation was determined using a Cell Death Detection enzyme-linked immunosorbent assay (ELISA) kit. Annexin V-biotinylated vehicle- or NGN-treated cells were fractionated by subcellular fractionation centrifugation to isolate the plasma membrane (M) fraction. The levels of the indicated proteins in the lysates of (−)-, NGN-, -Z-VAD-FMK, and the NGN plus Z-VAD-FMK co-treated M fraction were determined by Western blot analysis using streptavidin-horseradish peroxidase (HRP) and specific antibody to Annexin V or cadherin. Antibody against cadherin was used as an internal control for the plasma membrane. The levels of phosphorylated histone H2A.X (Ser 139) (p-γ-H2AX (Ser 139)), H2AX, and caspase-3 in the total cell (T) lysates were determined by Western blot analysis with specific antibodies. β-Actin was used as an internal control for sample loading. (<b>G</b>,<b>H</b>) The effects of NGN on glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). Cells treated with vehicle or NGN (160 μM) for the indicated periods. The oxygen consumption rate (OCR) was measured in the presence of oligomycin-A (Oligo-A) (1 μM), carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP) (0.5 μM), and rotenone (Rot) (30 μM) plus myxothiazol (Myx) (10 μM) at the indicated time points. The extracellular acidification rate (ECAR) was examined under the sequential addition of glucose, Oligo-A (1 μM), and 2-deoxy-D-glucose (2-DG) (25 mM) at the indicated time points. The OCR and ECAR were measured using a Seahorse Bioscience XF24 Analyzer. (<b>I</b>–<b>M</b>) The effects of NGN on the levels of glucose uptake, pyruvate, lactate, ATP, and mitochondrial DNA (mtDNA) copy number. After 36 h of treatment with (−) or NGN (160 μM), the pyruvate, lactate, and ATP values were analyzed using the Pyruvate Assay kit, Lactate Assay kit, and ATP-based CellTiter-Glo Luminescent Cell Viability kit, respectively. Glucose uptake was measured using the Glucose Uptake Colorimetric assay kit. The level of mtDNA was analyzed using quantitative real-time PCR (qRT-PCR). The mtDNA expression was determined relative to that of β-actin. The values are presented as three independent experiments’ mean ± standard error. * <span class="html-italic">p</span> < 0.05: significantly different from vehicle- or NGN-treated cells.</p> "> Figure 2
<p>Decreased level of kirsten rat sarcoma viral oncogene homolog (KRAS) in the lipid rafts causes attenuation in the formation of lipid raft-associated KRAS–phosphatidylinositol 3-kinase (PI3K)–active GTP-binding Ras-related C3 botulinum toxin substrate (GTP-Rac1) complexes. (<b>A</b>) Nasopharyngeal carcinoma (NPC) cells were treated with vehicle (−) or naringenin (NGN) for 36 h. Detergent-resistant membrane (DRM) and detergent-soluble (DS) fractions were prepared by flotation along a sucrose density gradient. The levels of the indicated proteins in the lysates of (−)- or NGN-treated DRM and DS fractions and total cell (T) lysates were determined by Western blot analysis using specific antibodies. Antibodies against caveolin-1/CD55 and CD71 were used as internal controls for DRM and DS fractions. (<b>B</b>,<b>C</b>) After 36 h of treatment with (−) or NGN, DRM fractions were prepared by flotation along a sucrose density gradient. The antibody used for coimmunoprecipitation is indicated at the top. The proteins from the immunoprecipitated complexes were detected using Western blotting with specific antibodies. Normal IgG was used as a control for antibody specificity. Total and DRM lysates from (−)- or NGN-treated cells were used to monitor the indicated protein levels and were determined using Western blot analysis with specific antibodies.</p> "> Figure 3
<p>Disruption of kirsten rat sarcoma viral oncogene homolog (KRAS)–phosphatidylinositol 3-kinase (PI3K)–active GTP-binding Ras-related C3 botulinum toxin substrate (GTP-Rac1) complex formation and impaired energetic synthesis of the glycolysis and mitochondrial respiration pathways. (<b>A</b>–<b>C</b>) At 12 h after transfection with hemagglutinin (HA)-KRAS, GFP short hairpin RNA (shRNA), or KRAS shRNA, cells were treated with vehicle (−) or naringenin (NGN) for 36 h. The levels of the indicated proteins in the lysates of the total cell (T), detergent-resistant membrane (DRM), and detergent-soluble (DS) fractions were determined by Western blot analysis using specific antibodies. Co-immunoprecipitation of KRAS, p85α, p110α, and GTP-Rac1 was performed using the DRM fractions prepared from the cells treated as described above. The KRAS antibody used for co-immunoprecipitation is indicated at the top. The proteins from the immunoprecipitated complexes were detected using Western blotting with specific antibodies. Normal IgG was used as a control for antibody specificity. (<b>D</b>,<b>E</b>) Oxygen consumption rate (OCR) was measured in the presence of oligomycin-A (Oligo-A), carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and rotenone (Rot) plus myxothiazol (Myx) at the indicated time points. Extracellular acidification rate (ECAR) was examined in the sequential addition of glucose, Oligo-A, and 2-deoxy-D-glucose (2-DG) at the indicated time points. The OCR and ECAR were measured using a Seahorse Bioscience XF24 Analyzer. (<b>F</b>–<b>I</b>) The pyruvate, lactate, and ATP values were analyzed using the Pyruvate Assay kit, Lactate Assay kit, and ATP-based CellTiter-Glo Luminescent Cell Viability kit, respectively. In addition, glucose uptake was measured using the Glucose Uptake Colorimetric assay kit. The values are presented as three independent experiments’ mean ± standard error. * <span class="html-italic">p</span> < 0.05: significantly different from vehicle-treated empty vector-transfected, vehicle-treated GFP-transfected, or NGN-treated empty vector-transfected cells.</p> "> Figure 4
<p>Metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation associated with <span class="html-italic">lethal-7g</span> (<span class="html-italic">let-7g</span>)-attenuated kirsten rat sarcoma viral oncogene homolog (KRAS)–phosphatidylinositol 3-kinase (PI3K)–Ras-related C3 botulinum toxin substrate (Rac1)–protein kinase B (Akt) signaling. (<b>A</b>) Cells were treated with vehicle (−) or naringenin (NGN) for 36 h. The expression of <span class="html-italic">let-7</span> was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The <span class="html-italic">let-7</span> value was normalized to the U6 level. The Y-axis shows the denary logarithm of the normalized <span class="html-italic">let-7</span> copy number. (<b>B</b>,<b>C</b>) The effects of the protein kinase C (PKC) inhibitor chelerythrine (CHE) on <span class="html-italic">let-7g</span> and <span class="html-italic">OCT-1</span> expression. After treating with CHE (0.5 μM) for 36 h, the relative expression levels of <span class="html-italic">let-7g</span> and <span class="html-italic">OCT-1</span> were determined by qRT-PCR. The <span class="html-italic">let-7g</span> and <span class="html-italic">OCT-1</span> values were normalized to the U6 level and β-actin, respectively. The Y-axis shows the denary logarithm of the normalized <span class="html-italic">let-7g</span> or <span class="html-italic">OCT-1</span> copy number. (<b>D</b>–<b>F</b>) At 12 h after transfection with the negative (N) mimic control, <span class="html-italic">let-7g</span> mimic, (N) mimic control inhibitor, or <span class="html-italic">let-7g</span> inhibitor, cells were treated with (−) or NGN for 36 h. Five mM bismaleimidohexane (BMH)-treated cells were subjected to subcellular fractionation to obtain the mitochondrial (Mt) and endoplasmic reticulum (ER)/microsomal (Ms) fractions. In total, 20 μg of total protein from the recovered fractions was analyzed by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and probed with specific antibodies, as indicated. Cytochrome <span class="html-italic">c</span> oxidase subunit II (Cox-2), calnexin, and α-tubulin were used as internal controls for the mitochondria, ER, and cytosol, respectively. The levels of the indicated proteins in the total cell (T) lysates were determined by Western blot analysis using specific antibodies. (<b>G</b>,<b>H</b>) At 12 h after transfection with the (N) mimic control, <span class="html-italic">let-7g</span> mimic, (N) mimic control inhibitor, or <span class="html-italic">let-7g</span> inhibitor, cells were treated with (−) or NGN in the presence of 1 μM oligomycin-A (Oligo-A), carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and rotenone (Rot) plus myxothiazol (Myx) or the sequential addition of glucose, Oligo-A, and 2-DG at the indicated time points. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured using a Seahorse Bioscience XF24 Analyzer. (<b>I</b>,<b>J</b>) At 12 h after transfection with the (N) mimic control, <span class="html-italic">let-7g</span> mimic, (N) mimic control inhibitor, or <span class="html-italic">let-7g</span> inhibitor, cells were treated with vehicle (−), NGN, NGN plus Mitoquinone (MitoQ) (10 μM), decyltriphenylphosphonium bromide (DecylTPP) (1 μM), NGN plus dantrolene (25 μM), or NGN plus ruthenium red (1 μM) for 36 h. Flow cytometry determined the levels of mitochondrial reactive oxygen species (ROS) and cytosolic calcium (Ca<sup>++</sup>) by measuring the increased fluorescence. (<b>K</b>–<b>O</b>) Transfected cells were harvested 36 h after treatment with (−) or NGN. The glucose, pyruvate, lactate, and ATP values were analyzed using the Glucose assay, Pyruvate Assay kit, Lactate Assay kit, and ATP-based CellTiter-Glo Luminescent Cell Viability kit, respectively. In addition, glucose uptake was measured using the Glucose Uptake Colorimetric Assay kit. The values are presented as three independent experiments’ mean ± standard error. * <span class="html-italic">p</span> < 0.05: significantly different from vehicle-treated empty vector-transfected, vehicle-treated (N) mimic control-transfected, or vehicle-treated (N) mimic control inhibitor-transfected cells.</p> "> Figure 4 Cont.
<p>Metabolic dysfunction of glycolysis and mitochondrial oxidative phosphorylation associated with <span class="html-italic">lethal-7g</span> (<span class="html-italic">let-7g</span>)-attenuated kirsten rat sarcoma viral oncogene homolog (KRAS)–phosphatidylinositol 3-kinase (PI3K)–Ras-related C3 botulinum toxin substrate (Rac1)–protein kinase B (Akt) signaling. (<b>A</b>) Cells were treated with vehicle (−) or naringenin (NGN) for 36 h. The expression of <span class="html-italic">let-7</span> was determined using quantitative real-time polymerase chain reaction (qRT-PCR). The <span class="html-italic">let-7</span> value was normalized to the U6 level. The Y-axis shows the denary logarithm of the normalized <span class="html-italic">let-7</span> copy number. (<b>B</b>,<b>C</b>) The effects of the protein kinase C (PKC) inhibitor chelerythrine (CHE) on <span class="html-italic">let-7g</span> and <span class="html-italic">OCT-1</span> expression. After treating with CHE (0.5 μM) for 36 h, the relative expression levels of <span class="html-italic">let-7g</span> and <span class="html-italic">OCT-1</span> were determined by qRT-PCR. The <span class="html-italic">let-7g</span> and <span class="html-italic">OCT-1</span> values were normalized to the U6 level and β-actin, respectively. The Y-axis shows the denary logarithm of the normalized <span class="html-italic">let-7g</span> or <span class="html-italic">OCT-1</span> copy number. (<b>D</b>–<b>F</b>) At 12 h after transfection with the negative (N) mimic control, <span class="html-italic">let-7g</span> mimic, (N) mimic control inhibitor, or <span class="html-italic">let-7g</span> inhibitor, cells were treated with (−) or NGN for 36 h. Five mM bismaleimidohexane (BMH)-treated cells were subjected to subcellular fractionation to obtain the mitochondrial (Mt) and endoplasmic reticulum (ER)/microsomal (Ms) fractions. In total, 20 μg of total protein from the recovered fractions was analyzed by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and probed with specific antibodies, as indicated. Cytochrome <span class="html-italic">c</span> oxidase subunit II (Cox-2), calnexin, and α-tubulin were used as internal controls for the mitochondria, ER, and cytosol, respectively. The levels of the indicated proteins in the total cell (T) lysates were determined by Western blot analysis using specific antibodies. (<b>G</b>,<b>H</b>) At 12 h after transfection with the (N) mimic control, <span class="html-italic">let-7g</span> mimic, (N) mimic control inhibitor, or <span class="html-italic">let-7g</span> inhibitor, cells were treated with (−) or NGN in the presence of 1 μM oligomycin-A (Oligo-A), carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and rotenone (Rot) plus myxothiazol (Myx) or the sequential addition of glucose, Oligo-A, and 2-DG at the indicated time points. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured using a Seahorse Bioscience XF24 Analyzer. (<b>I</b>,<b>J</b>) At 12 h after transfection with the (N) mimic control, <span class="html-italic">let-7g</span> mimic, (N) mimic control inhibitor, or <span class="html-italic">let-7g</span> inhibitor, cells were treated with vehicle (−), NGN, NGN plus Mitoquinone (MitoQ) (10 μM), decyltriphenylphosphonium bromide (DecylTPP) (1 μM), NGN plus dantrolene (25 μM), or NGN plus ruthenium red (1 μM) for 36 h. Flow cytometry determined the levels of mitochondrial reactive oxygen species (ROS) and cytosolic calcium (Ca<sup>++</sup>) by measuring the increased fluorescence. (<b>K</b>–<b>O</b>) Transfected cells were harvested 36 h after treatment with (−) or NGN. The glucose, pyruvate, lactate, and ATP values were analyzed using the Glucose assay, Pyruvate Assay kit, Lactate Assay kit, and ATP-based CellTiter-Glo Luminescent Cell Viability kit, respectively. In addition, glucose uptake was measured using the Glucose Uptake Colorimetric Assay kit. The values are presented as three independent experiments’ mean ± standard error. * <span class="html-italic">p</span> < 0.05: significantly different from vehicle-treated empty vector-transfected, vehicle-treated (N) mimic control-transfected, or vehicle-treated (N) mimic control inhibitor-transfected cells.</p> "> Figure 5
<p><span class="html-italic">Lethal-7g</span> (<span class="html-italic">let-7g</span>) upregulation attenuates glucose transporter-1 (GLUT-1) lipid raft membrane-targeting without affecting hypoxia-inducible factor 1α (HIF-1α)-mediated pyruvate kinase type M2 (PKM2), pyruvate dehydrogenase kinase 1 (PDK1), hexokinase II (HK-II), lactate dehydrogenase (LDH), and succinate dehydrogenase (SDH) activities. (<b>A</b>–<b>I</b>) At 12 h after transfection with the negative (N) mimic control, <span class="html-italic">let-7g</span> mimic, (N) mimic control inhibitor, or <span class="html-italic">let-7g</span> inhibitor, cells treated with vehicle (−) or naringenin (NGN) for 36 h. The levels of the indicated proteins in the total cell (T) lysates or detergent-resistant membrane (DRM) fractions were determined by Western blot analysis using specific antibodies. The FKM2, PDK1, HK-II, LDH, and SDH activities were analyzed using the Colorimetric-Based Pyruvate Kinase Activity Assay, ADP-GloTM Kinase Assay, Colorimetric Hexokinase Activity Assay, Lactate Dehydrogenase Assay, and Succinate Dehydrogenase Activity Colorimetric Assay, respectively. The Succinate Colorimetric Assay kit determined the succinate level. β-Actin was used as an internal control for sample loading. * <span class="html-italic">p</span> < 0.05.</p> "> Figure 6
<p>Suppression of monocyte chemoattractant protein-induced protein-1 (MCPIP1)-mediated degradation of <span class="html-italic">lethal-7g</span> (<span class="html-italic">let-7g</span>) by naringenin (NGN) involved the attenuation of glycolysis and mitochondrial mitochondrial oxidative phosphorylation (OXPHOS). (<b>A</b>,<b>B</b>) Immunoprecipitated MCPIP1 (IP:MCPIP1) from the nasopharyngeal carcinoma (NPC) or Smulow–Glickman (S-G) cells and recombinant purified MCPIP1 (rMCPIP1) used in the experiments. The inhibition of the <span class="html-italic">let-7g</span> degradation of MCPIP1-mediated by NGN, performed by in vitro RNA cleavage assay and analyzed by Northern blotting (NB). The levels of the IP:MCPIP1 or rMCPIP1 in reactions were determined by Western blot (WB) analysis using specific antibodies. (<b>C</b>–<b>E</b>) At 12 h after transfection with FLAG-MCPIP1, FLAG-MCPIP1 (D141N), or MCPIP1 short hairpin RNA (shRNA), cells were treated with vehicle (−) or NGN in the presence of 1 μM oligomycin-A (Oligo-A), carbonylcyanide-p-trifluoromethoxyphenylhydrazone (FCCP), and rotenone (Rot) plus myxothiazol (Myx) or the sequential addition of glucose, Oligo-A, and 2-deoxy-D-glucose (2-DG) at the indicated time points. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured using a Seahorse Bioscience XF24 Analyzer. Western blot analysis using specific antibodies determined the levels of the indicated proteins in the total cell lysates. Quantitative real-time polymerase chain reaction (qRT-PCR) determined the relative expression level of <span class="html-italic">let-7g.</span> The <span class="html-italic">let-7g</span> value was normalized to the U6 level. The Y-axis shows the denary logarithm of the normalized <span class="html-italic">let-7g</span> copy number. The values are presented as three independent experiments’ mean ± standard error. * <span class="html-italic">p</span> < 0.05: significantly different from (−)-treated empty vector-transfected, NGN-treated empty vector-transfected, (−)-treated FLAG-MCPIP1-transfected, or (−)-treated MCPIP1 shRNA-transfected cells.</p> "> Figure 7
<p>A molecular model for the naringenin (NGN)-induced impairment of the mitochondria-mediated bioenergetics in nasopharyngeal carcinoma (NPC) cells. (<b>A</b>) The selective interaction of argonaute (AG) protein or an undefined factor with monocyte chemoattractant protein-induced protein-1 (MCPIP1) may accomplish the sequence-specific targeting of <span class="html-italic">pre-lethal-7g</span> (<span class="html-italic">pre-let-7g</span>) and promote MCPIP1-mediated <span class="html-italic">pre-let-7g</span> degradation to decrease the biogenesis of <span class="html-italic">let-7g</span>, resulting in the attenuation of the <span class="html-italic">let-7g</span>-mediated translational repression of kirsten rat sarcoma viral oncogene homolog (<span class="html-italic">KRAS</span>) mRNA. The resultant elevated KRAS increases the formation of clustered KRAS- phosphatidylinositol 3-kinase (PI3K)-active GTP-binding Ras-related C3 botulinum toxin substrate (GTP-Rac1)–protein kinase B (Akt) signaling molecules in the lipid raft membranes, constituting a central element in the initiation of the coordination of glycolysis with mitochondrial oxidative phosphorylation (OXPHOS) for ATP generation. (<b>B</b>) Under the condition of the cellular uptake of NGN, NGN may bind to the AG protein or an undefined cofactor to block the degradation of <span class="html-italic">pre-let-7g</span> by MCPIP1, increasing the level of <span class="html-italic">let-7g</span>, thus inducing the <span class="html-italic">let-7g</span>-mediated translational repression of <span class="html-italic">KRAS</span> mRNA and thereby dismissing the interaction between KRAS and p110α in the lipid raft membrane. The absence of KRAS in the p85α–p110α complexes causes the destabilization of p85α–p110α complexes in the lipid raft membrane. The resultant loss of the KRAS–p85α–p110α complexes in the lipid raft membrane leads to blocking PI3K-GTP-Rac1-mediated Akt activation. Attenuated Akt impaired the aerobic glycolysis and mitochondria-regulated bioenergetic functions in NPC cells.</p> ">
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Chemicals, Reagents, and Plasmids
2.3. Antibodies
2.4. Measurement of DNA Fragmentation
2.5. Rac1 Activation Assay
2.6. Measurement of the Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR)
2.7. Glucose Uptake Assay
2.8. Measurement of Cellular ATP
2.9. Measurement of Cellular Pyruvate and Lactate
2.10. Measurement of Mitochondrial ROS Production
2.11. Measurement of Intracellular Glucose
2.12. Measurement of Cytosolic Calcium (Ca++)
2.13. Determination of Let-7 Expression by Quantitative Real-Time PCR
2.14. In Vitro RNA Cleavage Assay
2.15. Pyruvate Kinase Type M2 (PKM2) Activity Assay
2.16. Pyruvate Dehydrogenase Kinase 1 (PDK1) Activity Assay
2.17. Hexokinase II (HK-II) Activity Assay
2.18. Lactate Dehydrogenase (LDH) Activity Assay
2.19. Succinate Dehydrogenase (SDH) Activity Assay
2.20. Determination of Succinate
2.21. Mitochondrial DNA (mtDNA) Copy Number
2.22. Statistical Analysis
3. Results
3.1. The Impairment of the Regulation of Glycolysis and Mitochondrial Oxidative Phosphorylation (OXPHOS) Confers the Apoptotic Death of NPC Cells
3.2. Decreased Interaction of KRAS with p110α by NGN Confers the Suppression of Lipid Raft-Associated KRAS–PI3K–Rac1–Akt-Mediated Bioenergetic Generation
3.3. NGN-Induced KRAS–PI3K–Rac1–Akt-Modulated Metabolic Dysfunction of Glycolysis and Mitochondrial OXPHOS Associated with the Up-Regulation of let-7g
3.4. Let-7g Upregulation-Induced Suppression of Lipid Raft-Associated GLUT-1 Is Involved in the Inhibition of Glycolytic and Mitochondrial OXPHOS Activity
3.5. NGN Inhibited the MCPIP1-Mediated Degradation of let-7g
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
Adenosine triphosphate | ATP |
B cell lymphoma 2 | BCL-2 |
Bcl-2-antagonist of cell death | BAD |
Bcl-2 antagonist killer 1 | BAK |
Bcl-2-associated x protein | BAX |
BCL-2/B-cell lymphoma-extra large | BCL-xL |
Cyclin dependent kinase 1 | CDK1 |
Detergent-resistant membranes | DRM |
Detergent-soluble | DS |
Endoplasmic reticulum | ER |
Epstein–Barr virus | EBV |
Extracellular acidification rate | ECAR |
Glucose transporter-1 | GLUT-1 |
Hexokinase II | HK-II |
Hypoxia-inducible factor 1α | HIF-α |
Latent membrane protein 1 | LAMP1 |
Lethal-7 | let-7 |
MicroRNAs | miRNAs |
Mitochondrial DNA | mtDNA |
Mitochondrial oxidative phosphorylation | OXPHOS |
Monocyte chemoattractant protein-induced protein-1 | MCPIP1 |
Nasopharyngeal Carcinoma | NPC |
Oxygen consumption rate | OCR |
Phosphatase and tensin homolog deleted from chromosome 10 | PTEN |
Phosphatidylinositol 3-kinase | PI3K |
Phosphatidylinositol-4,5-bisphosphate | PIP2 |
Phosphatidylinositol-3,4,5-trisphosphate | PIP3 |
Poly (ADP-ribose) polymerase | PARP |
Protein kinase B | Akt |
Protein kinase C | PKC |
Pyruvate dehydrogenase kinase 1 | PDK1 |
Pyruvate kinase type M2— | PKM2 |
Ras-related C3 botulinum toxin substrate 1 | Rac1 |
Short hairpin RNA | shRNA |
Succinate dehydrogenase | SDH |
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Hung, K.-C.; Tien, N.; Bau, D.-T.; Yao, C.-H.; Chen, C.-H.; Yang, J.-L.; Lin, M.-L.; Chen, S.-S. Let-7g Upregulation Attenuated the KRAS–PI3K–Rac1–Akt Axis-Mediated Bioenergetic Functions. Cells 2023, 12, 2313. https://doi.org/10.3390/cells12182313
Hung K-C, Tien N, Bau D-T, Yao C-H, Chen C-H, Yang J-L, Lin M-L, Chen S-S. Let-7g Upregulation Attenuated the KRAS–PI3K–Rac1–Akt Axis-Mediated Bioenergetic Functions. Cells. 2023; 12(18):2313. https://doi.org/10.3390/cells12182313
Chicago/Turabian StyleHung, Kuang-Chen, Ni Tien, Da-Tian Bau, Chun-Hsu Yao, Chan-Hung Chen, Jiun-Long Yang, Meng-Liang Lin, and Shih-Shun Chen. 2023. "Let-7g Upregulation Attenuated the KRAS–PI3K–Rac1–Akt Axis-Mediated Bioenergetic Functions" Cells 12, no. 18: 2313. https://doi.org/10.3390/cells12182313