Details

Autor(en) / Beteiligte

• Stiegelbauer, Verena
• Vychytilova-Faltejskova, Petra
• Karbiener, Michael
• Pehserl, Anna-Maria
• Reicher, Andreas
• Resel, Margit
• Heitzer, Ellen
• Ivan, Cristina
• Bullock, Marc
• Ling, Hui
• Deutsch, Alexander
• Wulf-Goldenberg, Annika
• Adiprasito, Jan Basri
• Stoeger, Herbert
• Haybaeck, Johannes
• Svoboda, Marek
• Stotz, Michael
• Hoefler, Gerald
• Slaby, Ondrej
• Calin, George Adrian
• Gerger, Armin
• Pichler, Martin

Titel

miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5

Ist Teil von

• Clinical cancer research, 2017-09, Vol.23 (17), p.5255-5266

Ort / Verlag

United States: American Association for Cancer Research Inc

Erscheinungsjahr

2017

Quelle

MEDLINE

Beschreibungen/Notizen

• miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer. miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation and The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments. Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts ( < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and and which in turn regulated colorectal cancer cell migration. The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. .