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

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posted on 2023-03-31, 20:02 authored by Verena Stiegelbauer, Petra Vychytilova-Faltejskova, Michael Karbiener, Anna-Maria Pehserl, Andreas Reicher, Margit Resel, Ellen Heitzer, Cristina Ivan, Marc Bullock, Hui Ling, Alexander Deutsch, Annika Wulf-Goldenberg, Jan Basri Adiprasito, Herbert Stoeger, Johannes Haybaeck, Marek Svoboda, Michael Stotz, Gerald Hoefler, Ondrej Slaby, George Adrian Calin, Armin Gerger, Martin Pichler

Supplementary Material

Funding

Austrian Science Funds

Verein fﺮr Krebskranke of the Medical University of Graz

Oesterreichische National bank

Medical University of Graz

Hans und Blanca Moser Foundation

Czech Ministry of Health

CEITEC

BBMRI CZ

NIH/NCI

NCI

Melanoma Foundation

Miriam and Jim Mulva research funds

UT MD Anderson Cancer Center Brain SPORE

Leukemia SPORE

CLL Moonshot Flagship project

2015 Knowledge GAP MDACC

Owens Foundation

Estate of C.G. Johnson Jr.

History

ARTICLE 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.

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