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

J 2017

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

STIEGELBAUER, V., Petra VYCHYTILOVÁ, M. KARBIENER, A.M. PEHSERL, A. REICHER et. al.

Basic information

Original name

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

Authors

STIEGELBAUER, V. (40 Austria), Petra VYCHYTILOVÁ (203 Czech Republic, belonging to the institution), M. KARBIENER (40 Austria), A.M. PEHSERL (40 Austria), A. REICHER (40 Austria), M. RESEL (40 Austria), E. HEITZER (40 Austria), C. IVAN (40 Austria), M. BULLOCK (40 Austria), H. LING (40 Austria), A. DEUTSCH (40 Austria), A. WULF-GOLDENBERG (276 Germany), J.B. ADIPRASITO (40 Austria), H. STOEGER (40 Austria), J. HAYBAECK (276 Germany), M. SVOBODA (203 Czech Republic), M. STOTZ (40 Austria), G. HOEFLER (40 Austria), Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution), G.A. CALIN (40 Austria), A. GERGER (40 Austria) and M. PICHLER (40 Austria)

Edition

Clinical cancer research, Philadelphia, AMER ASSOC CANCER RESEARCH, 2017, 1078-0432

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 10.199

RIV identification code

RIV/00216224:14740/17:00100444

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1158/1078-0432.CCR-17-0023

UT WoS

000409037300031

Keywords in English

ACUTE LYMPHOBLASTIC-LEUKEMIA; MICRORNAS; EXPRESSION; PROGNOSIS; GROWTH; GENES; PROGRESSION

Abstract

V originále

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.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

90004, large research infrastructures

Name: BBMRI-CZ

Citovat

STIEGELBAUER, V., Petra VYCHYTILOVÁ, M. KARBIENER, A.M. PEHSERL, A. REICHER, M. RESEL, E. HEITZER, C. IVAN, M. BULLOCK, H. LING, A. DEUTSCH, A. WULF-GOLDENBERG, J.B. ADIPRASITO, H. STOEGER, J. HAYBAECK, M. SVOBODA, M. STOTZ, G. HOEFLER, Ondřej SLABÝ, G.A. CALIN, A. GERGER and M. PICHLER. miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5. Clinical cancer research. Philadelphia: AMER ASSOC CANCER RESEARCH, 2017, vol. 23, No 17, p. 5255-5266. ISSN 1078-0432. Available from: https://dx.doi.org/10.1158/1078-0432.CCR-17-0023.

@article{1411966,
   author = {Stiegelbauer, V. and Vychytilová, Petra and Karbiener, M. and Pehserl, A.M. and Reicher, A. and Resel, M. and Heitzer, E. and Ivan, C. and Bullock, M. and Ling, H. and Deutsch, A. and WulfandGoldenberg, A. and Adiprasito, J.B. and Stoeger, H. and Haybaeck, J. and Svoboda, M. and Stotz, M. and Hoefler, G. and Slabý, Ondřej and Calin, G.A. and Gerger, A. and Pichler, M.},
   article_location = {Philadelphia},
   article_number = {17},
   doi = {http://dx.doi.org/10.1158/1078-0432.CCR-17-0023},
   keywords = {ACUTE LYMPHOBLASTIC-LEUKEMIA; MICRORNAS; EXPRESSION; PROGNOSIS; GROWTH; GENES; PROGRESSION},
   language = {eng},
   issn = {1078-0432},
   journal = {Clinical cancer research},
   title = {miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5},
   url = {http://clincancerres.aacrjournals.org/content/23/17/5255},
   volume = {23},
   year = {2017}
}

TY  - JOUR
ID  - 1411966
AU  - 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.
PY  - 2017
TI  - miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5
JF  - Clinical cancer research
VL  - 23
IS  - 17
SP  - 5255-5266
EP  - 5255-5266
PB  - AMER ASSOC CANCER RESEARCH
SN  - 10780432
KW  - ACUTE LYMPHOBLASTIC-LEUKEMIA
KW  - MICRORNAS
KW  - EXPRESSION
KW  - PROGNOSIS
KW  - GROWTH
KW  - GENES
KW  - PROGRESSION
UR  - http://clincancerres.aacrjournals.org/content/23/17/5255
L2  - http://clincancerres.aacrjournals.org/content/23/17/5255
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 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.
ER  -

STIEGELBAUER, V., Petra VYCHYTILOVÁ, M. KARBIENER, A.M. PEHSERL, A. REICHER, M. RESEL, E. HEITZER, C. IVAN, M. BULLOCK, H. LING, A. DEUTSCH, A. WULF-GOLDENBERG, J.B. ADIPRASITO, H. STOEGER, J. HAYBAECK, M. SVOBODA, M. STOTZ, G. HOEFLER, Ondřej SLABÝ, G.A. CALIN, A. GERGER and M. PICHLER. miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5. \textit{Clinical cancer research}. Philadelphia: AMER ASSOC CANCER RESEARCH, 2017, vol.~23, No~17, p.~5255-5266. ISSN~1078-0432. Available from: https://dx.doi.org/10.1158/1078-0432.CCR-17-0023.

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