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Stiegelbauer, V; Vychytilova-Faltejskova, P; Karbiener, M; Pehserl, AM; Reicher, A; Resel, M; Heitzer, E; Ivan, C; Bullock, M; Ling, H; Deutsch, A; Wulf-Goldenberg, A; Adiprasito, JB; Stoeger, H; Haybaeck, J; Svoboda, M; Stotz, M; Hoefler, G; Slaby, O; Calin, GA; Gerger, A; Pichler, M.
miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5.
Clin Cancer Res. 2017; 23(17):5255-5266 Doi: 10.1158/1078-0432.CCR-17-0023 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz

Gerger Armin

Pichler Martin

Stiegelbauer Verena

Co-Autor*innen der Med Uni Graz

Adiprasito Jan Basri

Deutsch Alexander

Haybäck Johannes

Heitzer Ellen

Höfler Gerald

Karbiener Michael

Pehserl Anna-Maria

Resel Margit

Stöger Herbert

Stotz Michael

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Abstract:

Purpose: 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.Experimental Design: 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 in vitro and in vivo The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in silico target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments.Results: Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts (P < 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 HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration.Conclusions: 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. Clin Cancer Res; 23(17); 5255-66. ©2017 AACR. ©2017 American Association for Cancer Research.

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