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Dlouhé nekódující molekuly RNA jako regulátory mitogenem aktivované proteinkinázové dráhy (MAPK) v nádorech


Autoři: Tasharrofi Behnoosh;  Ghafouri-Fard Soudeh
Působiště autorů: Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Vyšlo v časopise: Klin Onkol 2018; 31(2): 95-102
Kategorie: Přehled
doi: https://doi.org/10.14735/amko201895

Souhrn

Úvod:
Mitogenem aktivovaná proteinkinázová dráha (MAPK) přispívá k regulaci mnoha buněčných funkcí, jako je proliferace a diferenciace buněk, mobilita a apoptóza. Extracelulární signálně regulovaná kináza 1/2 (ERK1/2), c-Jun N-terminální kináza (JNK) /p38 a ERK5 jsou tři hlavní moduly v této dráze. Kaskády Raf-ERK1/2 a JNK přispívají k proliferaci buněk, migraci a přežití a jsou hlavními regulátory maligního fenotypu. Tato dráha je sama regulována několika vnějšími signály, stejně jako bočními signály z jiných signálních drah, které vytvářejí komplexní síť. Dlouhé nekódující RNA (lncRNA) jako hlavní modulátory genové exprese na transkripční a posttranskripční úrovni a také regulují tuto dráhu. Kromě toho můžou lncRNA sloužit jako biomarker a cíl nových léčebných strategií u pacientů s nádory.

Cíl:
Prozkoumat roli lncRNA v regulaci dráhy MAPK.

Závěr:
Vzhledem k úloze této dráhy v patogenezi několika typů nádorů dochází ke změnám exprese lncRNA, které vedou ke změnám v dráze MAPK, což vede k inhibici apoptózy a indukci buněčné proliferace a migrace. Některé lncRNA se navíc podílejí na spojení mezi MAPK a jinými drahami souvisejícími s nádory, jako je dráha PI3K/Akt prostřednictvím regulace určitých sdílených proteinů mezi těmito drahami. Na základě dostupnosti některých protinádorových léčiv, modulujících tuto dráhu, by identifikace lncRNA, ovlivňující tuto dráhu pomohla při vytváření účinných terapií.

Klíčová slova:
RNA – dlouhé nekódování – mitogenem aktivované proteinové kinázy – signální transdukce

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských časopisů.

Obdrženo:
5. 12. 2017

Přijato:
5. 2. 2018


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