The process of carcinogenesis, mechanism and regulatory role of miRNA-21, miRNA-26B and miRNA-10b in breast cancer

U radu je opisan razvoj tumora dojki kroz genetske aspekte kancerogeneze te promjene koje se javljaju tijekom tih procesa. Onkogeni imaju važnu ulogu u progresiji tumora i njihovom aktivacijom započinje proliferacija tumorskih stanica. Tumor supresijski geni imaju funkciju inhibiranja nastanka tumora i genetske promjene na tim genima su kritične tijekom kancerogeneze. Poseban naglasak u ovom radu je stavljen na regulaciju tumor supresijskih gena i onkogena na posttranskripcijskoj razini putem cirkularnih nekodirajućih microRNA molekula. Uvođenjem kemijski sintetiziranog oligonukleotida anti-miR-21 inhibira se rast tumora, a povećana ekspresija miR-26b u tumorskim stanicama ima suprimirajuće djelovanje na staničnu proliferaciju. Pokazalo se da prekomjerena ekspresija MiR-10b ima izrazito invazivno djelovanje i pozitivno regulira staničnu migraciju tijekom metastaziranja. Otkrićem njihove specifične regulacijske uloge, stabilne i visoko senzitivne miRNA mogu poslužiti kao minimalno invazivni biomarkeri u dijagnostici i prognostici karcinoma dojki te kao potencijalni terapeutici.This paper describes the development of breast cancer through genetic aspects of carcinogenesis. Oncogenes play an important role in tumor progression and their activation enhance proliferation of tumor cells. The tumor suppression genes have the function of inhibiting tumors, therefore genetic alterations in these genes are critical during carcinogenesis. Emphasis in this study is placed on the regulation of tumor suppressor genes and oncogenes in the post-transcriptional level by circular non-coding microRNA molecules. The introduction of chemically synthesized oligonucleotides of anti-miR-21 inhibits the tumor growth, while the overexpression of miR-26b tumor cells has a suppressing effect on cell proliferation. It has been proved that overexpression of mir-10b has an extremely invasive activity and positively regulates cell migration during metastasis. The discovery of their specific regulatory role, stable and highly sensitive miRNA may serve as minimally invasive biomarkers in the diagnosis and prognosis of breast cancers as well as potential therapeutics