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.Základní údaje
Originální název
MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion
Autoři
MACHÁČKOVÁ, Táňa (203 Česká republika, domácí), Petra VYCHYTILOVÁ (203 Česká republika, domácí), Kamila SOUČKOVÁ (203 Česká republika, domácí), Karolína TRACHTOVÁ (203 Česká republika, domácí), Dominika BRCHNELOVÁ (703 Slovensko, domácí), Marek SVOBODA (203 Česká republika, domácí), Igor KISS (203 Česká republika, domácí), Vladimír PROCHÁZKA (203 Česká republika, domácí), Zdeněk KALA (203 Česká republika, domácí) a Ondřej SLABÝ (203 Česká republika, garant, domácí)
Vydání
Cancers, BASEL, MDPI, 2020, 2072-6694
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30204 Oncology
Stát vydavatele
Švýcarsko
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 6.639
Kód RIV
RIV/00216224:14740/20:00114747
Organizační jednotka
Středoevropský technologický institut
UT WoS
000602212100001
Klíčová slova anglicky
miR-215-5p; metastasis; colorectal cancer; focal adhesion; extracellular matrix-receptor interaction
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 15. 10. 2024 09:26, Ing. Martina Blahová
Anotace
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.
Návaznosti
GA16-18257S, projekt VaV |
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90091, velká výzkumná infrastruktura |
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