Disease Information

General Information of the Disease (ID: DIS00545)

• Name: Lung cancer
• ICD: ICD-11: 2C25

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

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: SREBP cleavage activating protein (SCAP) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Non-small cell lung carcinoma
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.24E-08; Fold-change: 3.83E-01; Z-score: 5.97E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Alcoholic liver disease; Activation; hsa04936
• Cell Pathway Regulation: Fatty acid metabolism; Activation; hsa01212
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H441 cells; Pericardial effusion; Homo sapiens (Human); CVCL_1561
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: We demonstrated that SREBP-1 and SCAP are highly expressed in NSCLC and are positively correlated with the aggressive phenotypes of NSCLC cells. In addition, downregulation of the expression of tumor-suppressing hsa-miR-497-5p, which predictively targets SREBP-1, was observed. We also demonstrated that SREBP-1/SCAP/FASN lipogenic signaling plays a key role in CSCs-like and chemoresistant NSCLC phenotypes, especially because the fatostatin or shRNA targeting of SREBP-1 significantly suppressed the viability, cisplatin resistance, and cancer stemness of NSCLC cells and because treatment induced the expression of hsa-miR-497.

Key Molecule: Sterol regulatory element-binding protein 1 (SREBP-1) [1]

• Metabolic Type: Lipid metabolism
• Resistant Disease: Non-small cell lung carcinoma [ICD-11: 2C25.Y]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Alcoholic liver disease; Activation; hsa04936
• Cell Pathway Regulation: Fatty acid metabolism; Activation; hsa01212
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: H441 cells; Pericardial effusion; Homo sapiens (Human); CVCL_1561
• Experiment for Molecule Alteration: qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: We demonstrated that SREBP-1 and SCAP are highly expressed in NSCLC and are positively correlated with the aggressive phenotypes of NSCLC cells. In addition, downregulation of the expression of tumor-suppressing hsa-miR-497-5p, which predictively targets SREBP-1, was observed. We also demonstrated that SREBP-1/SCAP/FASN lipogenic signaling plays a key role in CSCs-like and chemoresistant NSCLC phenotypes, especially because the fatostatin or shRNA targeting of SREBP-1 significantly suppressed the viability, cisplatin resistance, and cancer stemness of NSCLC cells and because treatment induced the expression of hsa-miR-497.

References

• Ref 1: Targeting the SREBP-1/Hsa-Mir-497/SCAP/FASN Oncometabolic Axis Inhibits the Cancer Stem-like and Chemoresistant Phenotype of Non-Small Cell Lung Carcinoma Cells. Int J Mol Sci. 2022 Jun 30;23(13):7283.