Hsa-miR-6165 downregulates insulin-like growth factor-1 receptor (IGF-1R) expression and enhances apoptosis in SW480 cells.
AKT signaling
IGF-1R
apoptosis
colorectal cancer
miR-6165
Journal
Biological chemistry
ISSN: 1437-4315
Titre abrégé: Biol Chem
Pays: Germany
ID NLM: 9700112
Informations de publication
Date de publication:
26 03 2020
26 03 2020
Historique:
received:
04
11
2018
accepted:
10
10
2019
pubmed:
9
11
2019
medline:
25
6
2021
entrez:
9
11
2019
Statut:
ppublish
Résumé
MicroRNAs are small non-coding RNAs that are implicated in various biological processes. Hsa-miR-6165 (miR-6165), located in the p75NTR gene, is known to induce apoptosis in human cell lines, but its mechanism of action is not fully understood yet. Here, we predicted the insulin-like growth factor 1 receptor (IGF-1R) gene as a bona fide target for miR-6165. The overexpression of miR-6165 in SW480 cells resulted in significant downregulation of IGF-1R expression as detected by real time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Also, it resulted in reduced transcript levels of AKT2, AKT3, PI3KR3, PI3KR5, CCND1, c-MYC and P21 genes detected by RT-qPCR analysis. In addition, a direct interaction between miR-6165 and a 3'UTR sequence of the IGF-1R gene was verified through a dual luciferase assay. Furthermore, miR-6165 and IGF-1R showed opposite patterns of expression during the neural differentiation process of NT2 cells. Annexin V analysis and MTT assay showed that miR-6165 overexpression was followed by increased apoptosis and reduced the viability rate of SW480 cells. Moreover, a lower expression level of miR-6165 was detected in high-grade colorectal tumors compared with low-grade tumors. Taken together, the results of our study suggest a tumor suppressive role of miR-6165 in colorectal cancer, which seems to take place by regulating IGF-1R gene expression.
Identifiants
pubmed: 31702994
doi: 10.1515/hsz-2018-0421
pii: hsz-2018-0421
doi:
Substances chimiques
IGF1R protein, human
0
MIRN6165 microRNA, human
0
MicroRNAs
0
Receptor, IGF Type 1
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
477-485Références
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