Disease Information

General Information of the Disease (ID: DIS00521)

• Name: Kidney cancer
• ICD: ICD-11: 2C90

Type(s) of Resistant Mechanism of This Disease

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Sunitinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: Mesoderm induction early response 2 (MIER2) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vivo Model: Patients with renal cell carcinoma who underwent partial or radical nephrectomy; Homo Sapiens
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Overall survival assay (OS); Disease-free survival assay (DFS)
• Mechanism Description: Mechanistically, MIER2 facilitated P53 deacetylation by binding to HDAC1. Acetylation modification augmented the DNA-binding stability and transcriptional function of P53, while deacetylation of P53 hindered the transcriptional process of PGC1A, leading to intracellular lipid accumulation in RCC.

Key Molecule: Phosphoserine aminotransferase 1 (PSAT1) [2]

• Metabolic Type: Amino acid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: 4-week-old malenude mice, SN12; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Mechanism Description: Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT5 increased the susceptibility of sunitinib-resistant cells.

Key Molecule: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Specifically, overexpression of MIER2 plays a pivotal role in enhancing lipid accumulation, promoting malignancy, and contributing to sunitinib resistance in RCC. This occurs through thedownregulationof PGC1A via the MIER2/HDAC1/P53 axis. Our findings highlight the potential significance of targeting HDAC1, and we propose that TSA, an HDAC2 inhibitor, may serve as a promising therapeutic compound for patients with sunitinib-resistant advanced RCC.

Key Molecule: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1A) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: OS-RC-2 cells; Kidney; Homo sapiens (Human); CVCL_E313
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Specifically, overexpression of MIER2 plays a pivotal role in enhancing lipid accumulation, promoting malignancy, and contributing to sunitinib resistance in RCC. This occurs through thedownregulationof PGC1A via the MIER2/HDAC1/P53 axis. Our findings highlight the potential significance of targeting HDAC1, and we propose that TSA, an HDAC4 inhibitor, may serve as a promising therapeutic compound for patients with sunitinib-resistant advanced RCC.

Key Molecule: Mesoderm induction early response 2 (MIER2) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 7Su3rd cells; Kidney; Homo sapiens (Human); N.A.
• In Vitro Model: CaSu3rd cells; Kidney; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Mechanistically, MIER2 facilitated P53 deacetylation by binding to HDAC1. Acetylation modification augmented the DNA-binding stability and transcriptional function of P53, while deacetylation of P53 hindered the transcriptional process of PGC1A, leading to intracellular lipid accumulation in RCC.

Key Molecule: Mesoderm induction early response 2 (MIER2) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Specifically, overexpression of MIER2 plays a pivotal role in enhancing lipid accumulation, promoting malignancy, and contributing to sunitinib resistance in RCC. This occurs through thedownregulationof PGC1A via the MIER2/HDAC1/P53 axis. Our findings highlight the potential significance of targeting HDAC1, and we propose that TSA, an HDAC1 inhibitor, may serve as a promising therapeutic compound for patients with sunitinib-resistant advanced RCC.

Key Molecule: Mesoderm induction early response 2 (MIER2) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Specifically, overexpression of MIER2 plays a pivotal role in enhancing lipid accumulation, promoting malignancy, and contributing to sunitinib resistance in RCC. This occurs through thedownregulationof PGC1A via the MIER2/HDAC1/P53 axis. Our findings highlight the potential significance of targeting HDAC1, and we propose that TSA, an HDAC3 inhibitor, may serve as a promising therapeutic compound for patients with sunitinib-resistant advanced RCC.

Key Molecule: Phosphoserine aminotransferase 1 (PSAT1) [2]

• Metabolic Type: Amino acid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells.

Key Molecule: Phosphoserine aminotransferase 1 (PSAT1) [2]

• Metabolic Type: Amino acid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A-498 cells; Kidney; Homo sapiens (Human); CVCL_1056
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT2 increased the susceptibility of sunitinib-resistant cells.

Key Molecule: Phosphoserine aminotransferase 1 (PSAT1) [2]

• Metabolic Type: Amino acid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SN12-PM6 cells; N.A.; Homo sapiens (Human); CVCL_9549
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT3 increased the susceptibility of sunitinib-resistant cells.

Key Molecule: Phosphoserine aminotransferase 1 (PSAT1) [2]

• Metabolic Type: Amino acid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 293 T cells; Blood; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT4 increased the susceptibility of sunitinib-resistant cells.

Key Molecule: Alanine-serine-cysteine transporter 2 (ASCT2) [3]

• Metabolic Type: Redox metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: In all three cell lines, qRT-PCR and Western blotting also showed overexpression of ASCT2 in sunitinib-resistant cells compared to sunitinib-sensitive cells (Figure 2a). When comparing the expression of ASCT2 among sunitinib-sensitive cells, ASCT2 was found to be highly expressed in 786-O compared to that in Caki-1 and ACHN (Figure 2a). Sunitinib-resistant cells had higher intracellular concentrations of glutamine metabolism (glutamine, glutamate, and alphaKG)

Key Molecule: Alanine-serine-cysteine transporter 2 (ASCT2) [3]

• Metabolic Type: Redox metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: In all three cell lines, qRT-PCR and Western blotting also showed overexpression of ASCT2 in sunitinib-resistant cells compared to sunitinib-sensitive cells (Figure 2a). When comparing the expression of ASCT2 among sunitinib-sensitive cells, ASCT2 was found to be highly expressed in 786-O compared to that in Caki-1 and ACHN (Figure 3a). Sunitinib-resistant cells had higher intracellular concentrations of glutamine metabolism (glutamine, glutamate, and alphaKG)

Key Molecule: Mesoderm induction early response 2 (MIER2) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: 4-week-old nude mice, with Caki-1 cells; Mice
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay; Tumor weight assay
• Mechanism Description: Specifically, overexpression of MIER2 plays a pivotal role in enhancing lipid accumulation, promoting malignancy, and contributing to sunitinib resistance in RCC. This occurs through thedownregulationof PGC1A via the MIER2/HDAC1/P53 axis. Our findings highlight the potential significance of targeting HDAC1, and we propose that TSA, an HDAC5 inhibitor, may serve as a promising therapeutic compound for patients with sunitinib-resistant advanced RCC.

Key Molecule: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB3 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Key Molecule: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 769-P cells; Kidney; Homo sapiens (Human); CVCL_1050
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB4 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Key Molecule: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB5 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Key Molecule: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB6 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Key Molecule: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Caki-2 cells; Kidney; Homo sapiens (Human); CVCL_0235
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB7 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Key Molecule: 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) [4]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Hk-2 cells; Kidney; Homo sapiens (Human); CVCL_0302
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Colony formation assay
• Mechanism Description: In view of renal cancer as a metabolic disease [4], PFKFB3 mediated glycolytic pathways should affect RCC development and progression. However, the regulating role of PFKFB3 in RCC glycolysis metabolism is rarely elucidated currently, much less in pRCC. Our study primarily demonstrated the abnormal expression profile of PFKFB3 in pRCC. Experimental assays further verified that PFKFB8 could promote renal cancer cell proliferation and migration in vitro, confirming its oncogenic potential in tumor progression.

Key Molecule: Mesoderm induction early response 2 (MIER2) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: ACHN cells; Pleural effusion; Homo sapiens (Human); CVCL_1067
• In Vitro Model: Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• In Vitro Model: Hk-2 cells; Kidney; Homo sapiens (Human); CVCL_0302
• In Vitro Model: OS-RC-2 cells; Kidney; Homo sapiens (Human); CVCL_E313
• In Vitro Model: Sunitinib-resistant 786-O cells; Kidney; Homo sapiens (Human); CVCL_1051
• In Vitro Model: Sunitinib-resistant Caki-1 cells; Kidney; Homo sapiens (Human); CVCL_0234
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Dose-response curve assay; CCK8 proliferation assay
• Mechanism Description: Mechanistically, MIER2 facilitated P53 deacetylation by binding to HDAC1. Acetylation modification augmented the DNA-binding stability and transcriptional function of P53, while deacetylation of P53 hindered the transcriptional process of PGC1A, leading to intracellular lipid accumulation in RCC.

Key Molecule: Mesoderm induction early response 2 (MIER2) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Renal cell carcinoma [ICD-11: 2C90.0]
• Resistant Drug: Sunitinib
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vivo Model: MIER2 overexpression mice; control mice; Mice
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Tumor volume assay
• Mechanism Description: Mechanistically, MIER2 facilitated P53 deacetylation by binding to HDAC1. Acetylation modification augmented the DNA-binding stability and transcriptional function of P53, while deacetylation of P53 hindered the transcriptional process of PGC1A, leading to intracellular lipid accumulation in RCC.

References

• Ref 1: MIER2/PGC1A elicits sunitinib resistance via lipid metabolism in renal cell carcinoma. J Adv Res. 2025 Apr;70:287-305.
• Ref 2: Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma. Exp Cell Res. 2024 Apr 1;437(1):113977.
• Ref 3: Elucidation and Regulation of Tyrosine Kinase Inhibitor Resistance in Renal Cell Carcinoma Cells from the Perspective of Glutamine Metabolism. Metabolites. 2024 Mar 19;14(3):170.
• Ref 4: Multi-omics and immunogenomics analysis revealed PFKFB3 as a targetable hallmark and mediates sunitinib resistance in papillary renal cell carcinoma: in silico study with laboratory verification. Eur J Med Res. 2024 Apr 15;29(1):236.