Next Article in Journal
Deregulation of Cell Death in Cancer: Recent Highlights
Next Article in Special Issue
Low MicroRNA-19b Expression Shows a Promising Clinical Impact in Locally Advanced Rectal Cancer
Previous Article in Journal
Bioenergetic Profiling of the Differentiating Human MDS Myeloid Lineage with Low and High Bone Marrow Blast Counts
Previous Article in Special Issue
MicroRNAs in Rectal Cancer: Functional Significance and Promising Therapeutic Value
 
 
Article

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

1
Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic
2
Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Faculty of Medicine, Masaryk University, 602 00 Brno, Czech Republic
3
Department of Surgery, Faculty Hospital Brno and Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
4
Department of Biology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(12), 3518; https://doi.org/10.3390/cancers12123518
Received: 13 November 2020 / Accepted: 23 November 2020 / Published: 26 November 2020
(This article belongs to the Special Issue microRNAs in Colorectal Cancer)
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. View Full-Text
Keywords: miR-215-5p; metastasis; colorectal cancer; focal adhesion; extracellular matrix-receptor interaction miR-215-5p; metastasis; colorectal cancer; focal adhesion; extracellular matrix-receptor interaction
Show Figures

Figure 1

MDPI and ACS Style

Machackova, T.; Vychytilova-Faltejskova, P.; Souckova, K.; Trachtova, K.; Brchnelova, D.; Svoboda, M.; Kiss, I.; Prochazka, V.; Kala, Z.; Slaby, O. MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion. Cancers 2020, 12, 3518. https://doi.org/10.3390/cancers12123518

AMA Style

Machackova T, Vychytilova-Faltejskova P, Souckova K, Trachtova K, Brchnelova D, Svoboda M, Kiss I, Prochazka V, Kala Z, Slaby O. MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion. Cancers. 2020; 12(12):3518. https://doi.org/10.3390/cancers12123518

Chicago/Turabian Style

Machackova, Tana, Petra Vychytilova-Faltejskova, Kamila Souckova, Karolina Trachtova, Dominika Brchnelova, Marek Svoboda, Igor Kiss, Vladimir Prochazka, Zdenek Kala, and Ondrej Slaby. 2020. "MiR-215-5p Reduces Liver Metastasis in an Experimental Model of Colorectal Cancer through Regulation of ECM-Receptor Interactions and Focal Adhesion" Cancers 12, no. 12: 3518. https://doi.org/10.3390/cancers12123518

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop