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

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Authors	STIEGELBAUER V. VYCHYTILOVÁ Petra KARBIENER M. PEHSERL A.M. REICHER A. RESEL M. HEITZER E. IVAN C. BULLOCK M. LING H. DEUTSCH A. WULF-GOLDENBERG A. ADIPRASITO J.B. STOEGER H. HAYBAECK J. SVOBODA M. STOTZ M. HOEFLER G. SLABÝ Ondřej CALIN G.A. GERGER A. PICHLER M.
Year of publication	2017
Type	Article in Periodical
Magazine / Source	Clinical cancer research
MU Faculty or unit	Central European Institute of Technology
Citation
Web	http://clincancerres.aacrjournals.org/content/23/17/5255
Doi	http://dx.doi.org/10.1158/1078-0432.CCR-17-0023
Keywords	ACUTE LYMPHOBLASTIC-LEUKEMIA; MICRORNAS; EXPRESSION; PROGNOSIS; GROWTH; GENES; PROGRESSION
Description	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 miR196b-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. (C) 2017 AACR.
Related projects:	CEITEC - Central European Institute of Technology