MiR-215-5p Reduces Liver Metastasis in an Experimental Model of
Colorectal Cancer through Regulation of ECM-Receptor
Interactions and Focal Adhesion

J 2020

MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion

MACHÁČKOVÁ, Táňa, Petra VYCHYTILOVÁ, Kamila SOUČKOVÁ, Karolína TRACHTOVÁ, Dominika BRCHNELOVÁ et. al.

Basic information

Original name

MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion

Authors

MACHÁČKOVÁ, Táňa (203 Czech Republic, belonging to the institution), Petra VYCHYTILOVÁ (203 Czech Republic, belonging to the institution), Kamila SOUČKOVÁ (203 Czech Republic, belonging to the institution), Karolína TRACHTOVÁ (203 Czech Republic, belonging to the institution), Dominika BRCHNELOVÁ (703 Slovakia, belonging to the institution), Marek SVOBODA (203 Czech Republic, belonging to the institution), Igor KISS (203 Czech Republic, belonging to the institution), Vladimír PROCHÁZKA (203 Czech Republic, belonging to the institution), Zdeněk KALA (203 Czech Republic, belonging to the institution) and Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Cancers, BASEL, MDPI, 2020, 2072-6694

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.639

RIV identification code

RIV/00216224:14740/20:00114747

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3390/cancers12123518

UT WoS

000602212100001

Keywords in English

miR-215-5p; metastasis; colorectal cancer; focal adhesion; extracellular matrix-receptor interaction

Abstract

V originále

Simple Summary Decreased expression of miR-215-5-p was found in tumor tissue of patients with colorectal cancer (CRC) in comparison to healthy colon tissue. Moreover, expression levels of miR-215-5p were further decreased in metastatic lesions compared to primary tumor tissue. Overall, CRC patients with lower expression of miR-215-5p in tumors had significantly shorter overall survival and a higher chance of metastasis. This study aimed to examine the effects of miR-215-5p supplementation on the metastatic potential of CRC. MiR-215-5p was found to decrease invasiveness, migratory capacity, tumorigenicity, and metastasis formation. Finally, transcriptome analysis identified signaling pathways involved in the process, and subsequent RT-qPCR validation indicates CTNNBIP1 to be a direct target of this microRNA. These results bring new insight into miR-215-5p biology, a molecule that could potentially serve as a promising target for CRC patients' future therapeutic strategies. Background: Growing evidence suggests that miR-215-5p is a tumor suppressor in colorectal cancer (CRC); however, its role in metastasis remains unclear. This study evaluates the effects of miR-215 overexpression on the metastatic potential of CRC. Methods: CRC cell lines were stably transfected with miR-215-5p and used for in vitro and in vivo functional analyses. Next-generation sequencing and RT-qPCR were performed to study changes on the mRNA level. Results: Overexpression of miR-215-5p significantly reduced the clonogenic potential, migration, and invasiveness of CRC cells in vitro and tumor weight and volume, and liver metastasis in vivo. Transcriptome analysis revealed mRNAs regulated by miR-215-5p and RT-qPCR confirmed results for seven selected genes. Significantly elevated levels of CTNNBIP1 were also observed in patients' primary tumors and liver metastases compared to adjacent tissues, indicating its direct regulation by miR-215-5p. Gene Ontology and KEGG pathway analysis identified cellular processes and pathways associated with miR-215-5p deregulation. Conclusions: MiR-215-5p suppresses the metastatic potential of CRC cells through the regulation of divergent molecular pathways, including extracellular-matrix-receptor interaction and focal adhesion. Although the specific targets of miR-215-5p contributing to the formation of distant metastases must be further elucidated, this miRNA could serve as a promising target for CRC patients' future therapeutic strategies.

Links

GA16-18257S, research and development project

Name: Studium mechanizmu spojeného s nádorově supresorovou funkcí miR-215 a substituce této miRNA jako nové lečebné strategie u kolorektálního karcinomu

Investor: Czech Science Foundation

90091, large research infrastructures

Name: NCMG

Citovat

MACHÁČKOVÁ, Táňa, Petra VYCHYTILOVÁ, Kamila SOUČKOVÁ, Karolína TRACHTOVÁ, Dominika BRCHNELOVÁ, Marek SVOBODA, Igor KISS, Vladimír PROCHÁZKA, Zdeněk KALA and Ondřej SLABÝ. MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion. Cancers. BASEL: MDPI, 2020, vol. 12, No 12, p. 1-21. ISSN 2072-6694. Available from: https://dx.doi.org/10.3390/cancers12123518.

@article{1744849,
   author = {Macháčková, Táňa and Vychytilová, Petra and Součková, Kamila and Trachtová, Karolína and Brchnelová, Dominika and Svoboda, Marek and Kiss, Igor and Procházka, Vladimír and Kala, Zdeněk and Slabý, Ondřej},
   article_location = {BASEL},
   article_number = {12},
   doi = {http://dx.doi.org/10.3390/cancers12123518},
   keywords = {miR-215-5p; metastasis; colorectal cancer; focal adhesion; extracellular matrix-receptor interaction},
   language = {eng},
   issn = {2072-6694},
   journal = {Cancers},
   title = {MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion},
   url = {https://www.mdpi.com/2072-6694/12/12/3518},
   volume = {12},
   year = {2020}
}

TY  - JOUR
ID  - 1744849
AU  - Macháčková, Táňa - Vychytilová, Petra - Součková, Kamila - Trachtová, Karolína - Brchnelová, Dominika - Svoboda, Marek - Kiss, Igor - Procházka, Vladimír - Kala, Zdeněk - Slabý, Ondřej
PY  - 2020
TI  - MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion
JF  - Cancers
VL  - 12
IS  - 12
SP  - 1-21
EP  - 1-21
PB  - MDPI
SN  - 20726694
KW  - miR-215-5p
KW  - metastasis
KW  - colorectal cancer
KW  - focal adhesion
KW  - extracellular matrix-receptor interaction
UR  - https://www.mdpi.com/2072-6694/12/12/3518
N2  - Simple Summary Decreased expression of miR-215-5-p was found in tumor tissue of patients with colorectal cancer (CRC) in comparison to healthy colon tissue. Moreover, expression levels of miR-215-5p were further decreased in metastatic lesions compared to primary tumor tissue. Overall, CRC patients with lower expression of miR-215-5p in tumors had significantly shorter overall survival and a higher chance of metastasis. This study aimed to examine the effects of miR-215-5p supplementation on the metastatic potential of CRC. MiR-215-5p was found to decrease invasiveness, migratory capacity, tumorigenicity, and metastasis formation. Finally, transcriptome analysis identified signaling pathways involved in the process, and subsequent RT-qPCR validation indicates CTNNBIP1 to be a direct target of this microRNA. These results bring new insight into miR-215-5p biology, a molecule that could potentially serve as a promising target for CRC patients' future therapeutic strategies. Background: Growing evidence suggests that miR-215-5p is a tumor suppressor in colorectal cancer (CRC); however, its role in metastasis remains unclear. This study evaluates the effects of miR-215 overexpression on the metastatic potential of CRC. Methods: CRC cell lines were stably transfected with miR-215-5p and used for in vitro and in vivo functional analyses. Next-generation sequencing and RT-qPCR were performed to study changes on the mRNA level. Results: Overexpression of miR-215-5p significantly reduced the clonogenic potential, migration, and invasiveness of CRC cells in vitro and tumor weight and volume, and liver metastasis in vivo. Transcriptome analysis revealed mRNAs regulated by miR-215-5p and RT-qPCR confirmed results for seven selected genes. Significantly elevated levels of CTNNBIP1 were also observed in patients' primary tumors and liver metastases compared to adjacent tissues, indicating its direct regulation by miR-215-5p. Gene Ontology and KEGG pathway analysis identified cellular processes and pathways associated with miR-215-5p deregulation. Conclusions: MiR-215-5p suppresses the metastatic potential of CRC cells through the regulation of divergent molecular pathways, including extracellular-matrix-receptor interaction and focal adhesion. Although the specific targets of miR-215-5p contributing to the formation of distant metastases must be further elucidated, this miRNA could serve as a promising target for CRC patients' future therapeutic strategies.
ER  -

MACHÁČKOVÁ, Táňa, Petra VYCHYTILOVÁ, Kamila SOUČKOVÁ, Karolína TRACHTOVÁ, Dominika BRCHNELOVÁ, Marek SVOBODA, Igor KISS, Vladimír PROCHÁZKA, Zdeněk KALA and Ondřej SLABÝ. MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion. \textit{Cancers}. BASEL: MDPI, 2020, vol.~12, No~12, p.~1-21. ISSN~2072-6694. Available from: https://dx.doi.org/10.3390/cancers12123518.

Detailed Information on Publication Record