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

• Published in: Clinical cancer research 2017-09, Vol.23 (17), p.5255-5266
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Cancer; Cell adhesion & migration; Cell Line, Tumor; Cell migration; Cell Movement - genetics; Cell Proliferation - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Disease-Free Survival; Experimental design; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Genetic transformation; Homeodomain Proteins - genetics; Humans; In vivo methods and tests; Male; Metastases; Metastasis; Mice; MicroRNAs - genetics; Middle Aged; N-Acetylgalactosaminyltransferases - genetics; Neoplasm Metastasis; Patients; Polypeptide N-acetylgalactosaminyltransferase; Target recognition; Tumor cell lines; Xenograft Model Antitumor Assays
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-17-0023

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. .