A549 AKCİĞER ADENOKARSİNOMU HÜCRELERİNDE CRISPR/CAS9 TABANLI KRAS GEN DÜZENLEME YAKLAŞIMLARI
15th INTERNATIONAL CONGRESS ON CURRENT DEVELOPMENTS IN SCIENCE, TECHNOLOGY AND SOCIAL SCIENCES, Paris, Fransa, 19 - 21 Haziran 2026, ss.261-269, (Tam Metin Bildiri)
- Yayın Türü: Bildiri / Tam Metin Bildiri
- Basıldığı Şehir: Paris
- Basıldığı Ülke: Fransa
- Sayfa Sayıları: ss.261-269
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Erciyes Üniversitesi Adresli: Evet
Özet
Cancer constitutes a complex group of diseases characterized by high mortality and morbidity, arising from the loss of control over cellular growth and proliferation mechanisms. Globally, lung cancer ranks first among cancer-related deaths, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all lung cancer cases. Among the genetic alterations implicated in NSCLC development, KRAS mutations are among the most frequently observed molecular events. The KRAS gene is a critical component of signal transduction networks involved in cellular proliferation, differentiation, and survival; specifically, mutations occurring at codon 12 play a crucial role in sustaining oncogenic activity. The KRAS G12S mutation is one of the key molecular alterations associated with tumor progression, treatment resistance, and poor prognosis. In recent years, advances in genome-editing technologies have enabled the development of novel approaches to cancer therapy. Among these technologies, the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) system has attracted significant attention in translational cancer research due to its high specificity in targeting and editing genomic regions. Direct targeting of driver oncogenes, such as KRAS, is considered a promising strategy to diminish the proliferative capacity of tumor the cells and enhance therapeutic sensitivity. This study aims to evaluate CRISPR/Cas9-mediated knockdown of the KRAS gene in the A549 lung adenocarcinoma cell line harbouring the KRAS G12S mutation, and to assess the resulting molecular effects in combination with afatinib administration. Plasmid constructs containing KRAS-targeted sgRNA will be transfected into the cells using various gene transfer methods. Genome editing efficiency and cellular responses will be comparatively evaluated; cell viability will be analysed via the MTT assay, genomic alterations via Sanger sequencing, gene expression levels via quantitative real-time PCR, and protein-level changes via Western blot analysis. This study is expected to demonstrate the therapeutic potential of the CRISPR/Cas9-based genome-editing approach in KRAS-mutant NSCLC, compare the efficiencies of different gene delivery systems, and provide novel insights into the potential synergistic effects of combination therapies with afatinib. The findings are expected to contribute to the development of personalised cancer treatments and provide a scientific basis for future clinical trials.