Format:
Online-Ressource
ISSN:
1437-4315
Content:
Abstract: TGFβ signaling is a known pathway to be involved in colorectal cancer (CRC) progression and miRNAs play crucial roles by regulating different components of this pathway. Hence, finding the link between miRNAs and the pathway could be beneficial for CRC therapy. Array data indicated that miR-186-5p is a differentially expressed miRNA in colorectal Tumor/Normal tissues and bioinformatics tools predicted SMAD6/7 (inhibitory SMADs) as bona fide targets of this miRNA. Here, we intended to investigate the regulatory effect of the miR-186-5p expression on TGFβ signaling in CRC. Firstly, the miR-186-5p overexpression in HCT116 cells resulted in a significant reduction of SMAD6/7 expression, measured through RT-qPCR. Then, the direct interactions of miR-186-5p with SMAD6/7 3′UTRs were supported through dual luciferase assay. Furthermore, miR-186-5p overexpression suppressed proliferation, cell viability, and migration while, it increased apoptosis in CRC cells, assessed by cell cycle, MTT, scratch and Annexin V/PI apoptosis assays. Consistently, miR-186-5p overexpression resulted in reduced CyclinD1 protein using western blot, and also resulted in increased P21 and decreased c-Myc expression. Overall, these results introduced miR-186-5p as a cell cycle suppressor through downregulation of SMAD6/7 expression. Thus, miR-186-5p might be served as a novel tumor suppressive biomarker and therapeutic target in CRC treatment.
In:
volume:402
In:
number:4
In:
year:2021
In:
pages:469-480
In:
extent:12
In:
Biological chemistry, Berlin [u.a.] : de Gruyter, 1996-, 402, Heft 4 (2021), 469-480 (gesamt 12), 1437-4315
Language:
English
DOI:
10.1515/hsz-2019-0407
URN:
urn:nbn:de:101:1-2024022313362680628786
URL:
https://doi.org/10.1515/hsz-2019-0407
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2024022313362680628786
URL:
https://d-nb.info/1321546998/34
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