ArticleInternational journal of molecular sciences2022
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.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Lipid Metabolic Reprogramming in Lung Cancer: Mechanisms and Therapeutic Targets in the Tumor Microenvironment.International journal of cancer · 2026Review
- Role of microRNAs in cisplatin response of cancer stem cells.Stem cell research & therapy · 2026Review
- The transcription factor ZNF217 drives hepatocellular carcinoma progression by activating de novo lipid synthesis via FASN upregulation.Journal of cancer research and clinical oncology · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Orchestration of the tumor microenvironment by citrus flavonoids: from preclinical mechanisms to translational therapeutic.Frontiers in immunology · 2026Review
- Unraveling the role of ChREBP in lung adenocarcinoma: Expression, regulatory networks, and potential functional impact.PloS one · 2026Article
- The regulatory role and mechanism of energy metabolism and immune response in head and neck cancer.Genes & diseases · 2025Review
- Wnt Signalling-Activated EN2 Promotes the Progression of Glioblastoma by Upregulating Fatty Acid Synthesis Metabolism.Journal of cellular and molecular medicine · 2025Article
- Non-Coding RNAs as Critical Modulators of Cholesterol Metabolism in Cancer.Biomedicines · 2025Review
- Review
- Comprehensive analysis of ceRNA Networks in UCEC: Prognostic and therapeutic implications.PloS one · 2025Article
- Targeting lipogenesis promotes the synergistic effect of the selective HDAC6 inhibitor ITF3756 with bortezomib in colon cancer cells.Frontiers in pharmacology · 2025Article
- Xingxiao Pill Suppressed the Progression of Non-Small Cell Lung Cancer by Targeting SREBP1/FASN-Induced Fatty Acid Biosynthesis via PI3K/AKT/mTOR Signaling Pathway.Cancer management and research · 2025Article
- Anthocyanins and flavonoids derived fromActa biochimica et biophysica Sinica · 2024Article
- The roles and mechanisms of SREBP1 in cancer development and drug response.Genes & diseases · 2024Review
- DPP3 promotes breast cancer tumorigenesis by stabilizing FASN and promoting lipid synthesis.Acta biochimica et biophysica Sinica · 2024Article
- Long non‑coding RNAs, lipid metabolism and cancer (Review).Experimental and therapeutic medicine · 2023Review
- PluriBAC: A Versatile Baculovirus-Based Modular System to Express Heterologous Genes in Different Biotechnological Platforms.Viruses · 2023Article
- A Systematic Role of Metabolomics, Metabolic Pathways, and Chemical Metabolism in Lung Cancer.Vaccines · 2023Review
- Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundLung cancer remains a leading cause of cancer-related death, with an annual global mortality rate of 18.4%. Despite advances in diagnostic and therapeutic technologies, non-small cell lung carcinoma (NSCLC) continues to be characterized by a poor prognosis. This may be associated with the enrichment of cancer stem cells (CSCs) and the development of chemoresistance-a double-edged challenge that continues to impede the improvement of long-term outcomes. Metabolic reprogramming is a new hallmark of cancer. Sterol regulatory element-binding proteins (SREBPs) play crucial regulatory roles in the synthesis and uptake of cholesterol, fatty acids, and phospholipids. Recent evidence has demonstrated that SREBP-1 is upregulated in several cancer types. However, its role in lung cancer remains unclear.
objectiveThis study investigated the role of SREBP-1 in NSCLC biology, progression, and therapeutic response and explored the therapeutic exploitability of SREBP-1 and SREBP-1-dependent oncometabolic signaling and miRNA epigenetic regulation.
methodsWe analyzed SREBP-1 levels and biological functions in clinical samples and the human NSCLC cell lines H441 and A549 through shRNA-based knock down of SREBP function, cisplatin-resistant clone generation, immunohistochemical staining of clinical samples, and cell viability, sphere-formation, Western blot, and quantitative PCR assays. We conducted in-silico analysis of miRNA expression in NSCLC samples by using the Gene Expression Omnibus (GSE102286) database.
resultsWe 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.
conclusionTargeting the SREBP-1/hsa-miR-497 signaling axis is a potentially effective anticancer therapeutic strategy for NSCLC.
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