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Invaze karcinomu prostaty je podporována nedostatkem NDRG1 vyvolaným miR-96-5p prostřednictvím regulace NF-κB


Autoři: A. A. Soror 1;  R. Eshagh 1;  M. R. Fahim 1;  A. Jamshidian 2,3;  G. H. Monfared 1,3
Působiště autorů: Department of Biology, Faculty of Biological Sciences, East Tehran Branch (Ghiamdasht), Islamic Azad University, Tehran, Iran 1;  Tehran Medical Genetics Laboratory, Tehran, Iran 2;  Molecular Genetic and Reproductive Biology Department, Kowsar Poly-clinic, Tehran, Iran 3
Vyšlo v časopise: Klin Onkol 2024; 37(2): 95-101
Kategorie: Přehledy
doi: https://doi.org/10.48095/ccko202495

Souhrn

Východiska: N-myc downstream-regulovaný gen 1 (NDRG1) má významnou funkci při progresi nádorů. U karcinomu prostaty (prostate cancer –⁠ PCa) však regulační mechanizmus NDRG1 zůstává nejasný. Materiál a metody: Hladiny exprese miR-96-5p a NDRG1 byly hodnoceny v buněčných liniích PCa a v tkáních prostaty a validovány ve veřejných databázích pomocí polymerázové řetězové reakce v reálném čase, analýzy western blot a imunohistochemie. Funkce miR-96-5p a NDRG1 byla zkoumána pomocí testů hojení ran a transwell testů in vitro a testu myšího xenoimplantátu in vivo. Dráha regulovaná pomocí NDRG1 byla testována technikou sekvenování nové generace. K detekci vztahu mezi miR-96-5p, NDRG1 a NF-kB dráhou byl použit imunofluorescenční test a test s luciferázou. Výsledky: Nadměrná exprese NDRG1 potlačuje migraci, invazi a epiteliálně-mezenchymální přechod (EMT) in vitro a inhibuje metastázy in vivo. Navíc miR-96-5p přispívá k deficitu NDRG1 a podporuje migraci a invazi buněk PCa. Kromě toho ztráta NDRG1 aktivuje dráhu NF-kB, která stimuluje fosforylaci p65 a IKBa a indukuje EMT v PCa. Závěr: MiR-96-5p podporuje migraci a invazi PCa tím, že cílí na NDRG1 a reguluje dráhu NF-kB.

Klíčová slova:

karcinom prostaty – NDRG1 – miR-96-5p – NF-kB – EMT


Zdroje

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