上皮-间质转换
癌症研究
细胞生长
MAPK/ERK通路
异位表达
细胞迁移
癌变
胰腺癌
基质凝胶
生物
细胞生物学
下调和上调
细胞
信号转导
转移
癌症
细胞培养
血管生成
基因
遗传学
生物化学
作者
Nilgün Gürbüz,Nermin Kahraman,Hafize Elif Sonmez,Hamada A. Mokhlis,Pınar Aslan Koşar,Bülent Özpolat
出处
期刊:Anti-cancer Agents in Medicinal Chemistry
[Bentham Science]
日期:2022-08-01
卷期号:22 (14): 2607-2618
被引量:1
标识
DOI:10.2174/1871520622666220117123213
摘要
Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer deaths in the US due to lack of effective targeted therapeutics and extremely poor prognosis. Objective: To investigate the role of miR-193b and related signaling mechanism in PDAC cell proliferation, invasion and tumor growth. Methods: Using PDAC cell lines we performed cell viability, colony formation, in vitro wound healing and matrigel invasion assays following transfection with miR-193b mimic or control-miR. To identify potential downstream targets of miR-193b we utilized miRNA-target prediction algorithms and investigate regulation of eukaryotic elongation factor-2 kinase (eEF2K) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways and mediators of epithelial mesenchymal transition (EMT) The role of miR-193b in PDAC tumorigenesis was evaluated in in vivo tumor growth of Panc-1 xenograft model in nude mice. Results: We found that miR-193b is under expressed in PDAC cells compared to corresponding normal pancreatic epithelial cells and demonstrated that ectopic expression of miR-193b reduced cell proliferation, migration and invasion and EMT through downregulation of eEF2K signaling in PDAC cells. miR-193b expression led to increased expression of E-Cadherin and Claudin-1, while decreasing Snail and TCF8/ZEB1 expressions via eEF2K and MAPK/ERK axis. In vivo systemic injection of miR-193b using lipid-nanoparticles twice a week reduced tumor growth of Panc-1 xenografts and eEF2K expression in nude mice. Conclusions: Our findings suggest that miR-193b expression suppresses PDAC cell proliferation, migration, invasion and EMT through inhibition of eEF2K/MAPK-ERK oncogenic axis and that miR-193b-based RNA therapy might be an effective therapeutic strategy to control growth of PDAC.
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