Indexed and abstracted in Science Citation Index Expanded and in Journal Citation Reports /Science Edition Bratisl Med J 2020; 121 (8) 554 – 557 DOI: 10.4149/BLL_2020_092 CLINICAL STUDY The role of miRNAs targeting K-ras and APC genes in colorectal cancer Yilmaz N 1,2 , Yilmaz U 1,3 , Tanbek K 3,4 , Arikan S 5 , Aksakal N 6 , Zeybek U 1 , Ergen A 1 Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. aergen@istanbul.edu.tr ABSTRACT OBJECTIVES: The occurrence of abnormal expression patterns in different types of cancer suggests that micro RNAs (miRNAs) may play an important role in tumorigenesis. The aim of this study was to examine the expression levels of miRNAs known to be associated with the regulation of the expression levels of the APC and K-ras, which are important in the development of colorectal cancer (CRC). METHODS: The expression levels of miR-27, miR-663, miR-217, miR-181d, APC and K-ras in the serum, tumor and adjacent tumor-free (healthy) tissues of the patients and serum of the healthy controls were investigated with qRT-PCR. RESULTS: Expression levels of miR-217, mR-181d, miR-663, miR-27 and K-ras were found to be higher in CRC tissues than in adjacent tumor-free tissues of the patients. In patient serum samples, miR-663 levels were statistically more elevated than in controls. In patient tumor tissues, miR-217, miR-181d and miR-27 expressions were found to be higher. CONCLUSIONS: Increased miR-181d and miR-217 expression levels are associated with increased K-ras expression in the tumor tissues, and the expression of K-ras, which takes part as an oncogene in the CRC development, might be regulated by these miRNAs (Tab. 4, Ref. 33). Text in PDF www.elis.sk KEYWORDS: colorectal, cancer, miRNA, APC, K-ras. 1 Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey, 2 Department of Anatomy, Faculty of Medicine, Inonu University, Malatya, Turkey, 3 Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey, 4 De- partment of Biochemistry, Faculty of Medicine, Inonu University, Malatya, Turkey, 5 Department of General Surgery, Istanbul Education and Research Hospital, Istanbul, Turkey, and 6 Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey Address for correspondence: A. Ergen, Prof, MD, Department of Mo- lecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakif Gureba Cad., Sehremini.Fatih 34093 Istanbul, Turkey. Phone: +90.2124142000, Fax: + 90.2125324171 Acknowledgement: The present work was supported by the Research Fund of Istanbul University (Project No. 20707). Introduction Cancers developed due to the cumulative accumulation of ge- netic and epigenetic changes occurring in the normal colonic muco- sa are called colorectal cancer (CRC). Mutations occur in the APC gene known to play an important role in cell cycle control, apopto- sis, migration and adhesion, thus causing some regions of the APC protein in the colon epithelial cells not to be encoded, which results in problems in the mechanisms regulating cell growth and division (1, 2). The APC gene mutation, the earliest identified mutation in the adenoma-carcinoma process, is thought to be an initiator in adenoma formation and is observed in 98% of cases of CRC (3–5). The K-ras mutation occurs immediately after the APC gene mutation in the adenoma to carcinoma process and is thought to increase the GTPase activity, which leads to an increase in cel- lular proliferation and malignant transformation in CRC deve- lopment (6, 7). MicroRNAs (miRNAs) are single-stranded, 18–24 nucleotides long, RNAs that do not encode proteins and are naturally produced in cells (8). Abnormal expression patterns of miRNAs that play a role in regulating the expression of genes that control cellular functions such as proliferation, differentiation and apoptosis in different types of cancer indicate that they take an important part in tumorigenesis (9). The demonstration of different expression patterns between the tumor and normal tissues suggests that there may be a direct relationship between miRNAs and cancer, and that they may have a potential as biomarkers in the diagnosis, classifi- cation and treatment of cancer (10, 11). The aim of this study was to examine the expression levels of miR-27, miR-663, miR-217, miR-181d, APC and K-ras in tumor and adjacent tumor-free (healthy) tissue samples of individuals with CRC. Expression levels of miR-27, miR-663, miR-217, and miR- 181d between tumor tissue and serum samples of CRC patients as well as between the serum samples of CRC patients and healthy controls were examined for the purpose of contributing to the deve- lopment of new miRNA-based methods in the diagnosis and treat- ment of CRC. Materials and methods Study Population CRC in the Department of General Surgery, Istanbul Fa- culty of Medicine, Istanbul University and 50 healthy indivi-