| Abstract | Različiti oblici raka jedan od najčešćih uzroka smrtnosti širom svijeta, a s obzirom da mnogi terapeutici vremenom gube djelotvornost, potrebno je razviti nove strategije liječenja. Mnoga istraživanja pokazala da se potencijalne terapije raka mogu bazirati na manipulacijama nad Sirt3, NAD+ ovisne deacetilaze dominantno smještene u mitohondrijima. Sirt3 kontrolira acetilacijski status proteina i tako regulira obranu stanice od stresa, produkciju reaktivnih kisikovih vrsta, metabolizam, ATP sintezu, stanični ciklus, apoptozu i proliferaciju zbog čega se naglašava njegova važna uloga u karcinogenezi. No, ovisno o specifičnom staničnom kontekstu, tj. vrsti raka kao i eksperimentalnim uvjetima, Sirt3 pokazuje ili onkogena ili tumor-supresorska svojstva iz čega proizlazi njegova dualnost. Stoga je cilj ovog rada razjasniti uloge Sirt3 u biologiji raka te objediniti poznate podatke i mehanizme kojima Sirt3 svojim proonkogenim i/ili tumor-supresorskim svojstvima utječe na proliferaciju, metabolizam, metastaziranje, upalu i angiogenezu raka. Na temelju obrađenih podataka za desetak vrsta tumora, može se zaključiti kako su različiti tumor-supresorski ili proonkogeni Sirt3-ovisni mehanizmi prisutni u različitim, ali i unutar istih tipova tumora što dodatno naglašava dualnost. Odnosno kroz aktivaciju i inhibiciju različitih signalnih puteva i/ili transkripcijskih faktora kao i kroz regulaciju razine oksidativnog oštećenja Sirt3 može kontrolirati ishod karcinogeneze pa tako kod raka pluća ne-malih stanica i oralnog raka djeluje kao onkogen, a kod raka pluća malih stanica, raka jetre, žučnih vodova i prostate pokazana je tumor-supresorska uloga. Posebno se zanimljivi rezultati za rak debelog crijeva, jajnika i dojke kod kojih je u različitim ekspreimentima potvrđena i proonkogena i tumor-supresorska uloga unutar istog tipa raka. |
| Abstract (english) | Cancer is one of the most frequent causes of mortality worldwide, and because of many cancer therapeutics lose their efficiency with time, it is urgent to develop novel curing strategies. Many researches have shown that potential therapies could be based on Sirtuin 3 (Sirt3) manipulation. Sirt3 is NAD+ dependent deacetylase dominantly located in mitochondria that controls protein-acetylation status in cells, regulates cellular stress response, reactive oxygen species (ROS) production, cell metabolism, ATP synthesis, cell cycle, apoptosis and proliferation, thus having a very important role in tumorigenesis. However, depending on the cellular context, type of cancer and experimental conditions Sirt3 can have a dual role – it can act as oncogene and/or tumor supressor. Therefore, aim of this paper is to elucidate roles of Sirt3 in cancer biology and to assemble known information and mechanisms on how Sirt3, with its oncogene or tumor supressor properties, affects cancer proliferation, metabolism, metastasis, inflamation and angiogenesis. Based on processed data for several cancer types, it could be concluded that different oncogene or tumor supressor Sirt3-depended mechanisms are present in the different, but also within the same types of cancer, which further emphasizes duality of Sirt3. Thus, through activation or inhibiton of various signling pathways and/or transcriptional factors along with oxidative damage regulation, Sirt3 controls outcome of carcinogenesis. For inastance, Sirt3 acts as oncogen in non-small cell lung cancer and oral cancer, whereas in small-cell lung cancer, hepatocelullar carcinoma, cholangiocarcinoma and prostate cancer as tumor suppressor. Results for colorectal, ovarian and breast cancer are especially interesting because researches have sho |
