TY - JOUR
T1 - MiR-196b-5p regulates colorectal cancer cell migration and metastases through interaction with HOXB7 and GALNT5
AU - Stiegelbauer, Verena
AU - Vychytilova-Faltejskova, Petra
AU - Karbiener, Michael
AU - Pehserl, Anna Maria
AU - Reicher, Andreas
AU - Resel, Margit
AU - Heitzer, Ellen
AU - Ivan, Cristina
AU - Bullock, Marc
AU - Ling, Hui
AU - Deutsch, Alexander
AU - Wulf-Goldenberg, Annika
AU - Adiprasito, Jan Basri
AU - Stoeger, Herbert
AU - Haybaeck, Johannes
AU - Svoboda, Marek
AU - Stotz, Michael
AU - Hoefler, Gerald
AU - Slaby, Ondrej
AU - Calin, George Adrian
AU - Gerger, Armin
AU - Pichler, Martin
N1 - Publisher Copyright:
© 2017 AACR.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-17-0023
DO - 10.1158/1078-0432.CCR-17-0023
M3 - Article
C2 - 28533224
AN - SCOPUS:85029357314
SN - 1078-0432
VL - 23
SP - 5255
EP - 5266
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -