Molecule Information

General Information of the Molecule (ID: Mol04131)

• Name: Mesoderm induction early response 2 (MIER2) ,Homo sapiens
• Molecule Type: Protein
• Gene Name: MIER2
• Gene ID: 54531
• Location: chr19:305573-344815[-]
• Sequence:
  MAEASSLGRQSPRVVSCLEHSLCPGEPGLQTTAVVSMGSGDHQFNLAEILSQNYSVRGEC
  EEASRCPDKPKEELEKDFISQSNDMPFDELLALYGYEASDPISDRESEGGDVAPNLPDMT
  LDKEQIAKDLLSGEEEEETQSSADDLTPSVTSHEASDLFPNRSGSRFLADEDREPGSSAS
  SDTEEDSLPANKCKKEIMVGPQFQADLSNLHLNRHCEKIYENEDQLLWDPSVLPEREVEE
  FLYRAVKRRWHEMAGPQLPEGEAVKDSEQALYELVKCNFNVEEALRRLRFNVKVIRDGLC
  AWSEEECRNFEHGFRVHGKNFHLIQANKVRTRSVGECVEYYYLWKKSERYDYFAQQTRLG
  RRKYVPSGTTDADQDLDGSDPDGPGRPRPEQDTLTGMRTDPLSVDGTAGGLDEPGVASDG
  LPSSEPGPCSFQQLDESPAVPLSHRPPALADPASYQPAVTAPEPDASPRLAVDFALPKEL
  PLISSHVDLSGDPEETVAPAQVALSVTEFGLIGIGDVNPFLAAHPTCPAPGLHSEPLSHC
  NVMTC
• Function: Transcriptional repressor. .
• Uniprot ID: MIER2_HUMAN
• Ensembl ID: ENSG00000105556
• HGNC ID: HGNC:29210

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  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)

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [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.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [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.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [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.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [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.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [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.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [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.

Disease Class: Renal cell carcinoma [ICD-11: 2C90.0] [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.