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  • Roles of Sirtuin-1 in Lung Cancer: From Tumor Progression to Targeted Therapy

  • Maryam Ashourpour,1,*
    1. Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran


  • Introduction: Sirtuins have different roles in several physiological and pathophysiological activities such as neurodegeneration, aging, obesity, age-related disorders, inflammation, cardiovascular diseases, and cancer. Among them, Sirtuin 1 (SIRT1) has garnered significant attention in the field of cancer research during the past ten years. SIRT1 acts as an NAD+-dependent deacetylase protein that influences vital genes involved in cancer development and progression, especially in lung cancer. The present review discusses the role of SIRT1 in lung cancer biology.
  • Methods: Between 2000 and 2026, the search was performed using the terms "SIRT1" and "lung cancer" across various databases, such as PubMed, Scopus, and Google Scholar.
  • Results: The reviewed research indicated that the expression of SIRT1 is altered in lung cancer and is linked with the number of features of tumor biology. The upregulation of SIRT1 has been found in cell lines and primary tumors of lung cancer and is correlated with shorter recurrence-free and overall survival rates. Moreover, SIRT1 overexpression was related to increased cellular proliferation, tumor metastasis, invasion, migration, epithelial–mesenchymal transition, and resistance to chemotherapy. The mechanism of action is based on the modulation of AMPK/mTOR, Ras/ERK, HIF-1α/VEGF, and Wnt/β-catenin signaling pathways by SIRT1. Several miRNAs, such as miR-217, miR-326, and miR-133a-3p, were demonstrated to influence lung cancer-related activities via SIRT1. SIRT1 suppression or downregulation diminished proliferation of lung cancer cells and promoted apoptosis or antitumor effect in various experimental models. On the other hand, other studies showed that activation of SIRT1 could decrease EMT, migration, and metastasis, meaning that the function of SIRT1 can be different depending on the cellular and molecular context. Overall, the reviewed evidence supports a multifunctional role of SIRT1 in the development and therapy of lung cancer.
  • Conclusion: SIRT1 participates in various molecular mechanisms linked to the progression of lung cancer, encompassing proliferation, invasion, EMT, metastasis, apoptosis, and resistance to treatment. Even though some studies have shown the tumor-promoting function of SIRT1 and proposed that its suppression could offer therapeutic benefits, other studies indicate that SIRT1 activation may have tumor-suppressive effects in specific contexts. Thus, the biological function of SIRT1 in lung cancer appears to be dependent on the specific context, necessitating additional research to elucidate the mechanisms that contribute to its varied effects and its viability as a therapeutic target.
  • Keywords: Sirtuin-1; Lung cancer; Therapeutics; Signaling pathways; Epigenetic regulation

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