miR1273g3p promotes proliferation, migration and invasion of LoVo cells via cannabinoid receptor 1 through activation of ERBB4/PIK3R3/mTOR/S6K2 signaling pathway.
Mol Med Rep
; 17(3): 4619-4626, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29328379
MicroRNAs (miR) are important in various crucial cell processes including proliferation, migration and invasion. Dysregulation of miRNAs have been increasingly reported to contribute to colorectal cancer. However, the detailed biological function and potential mechanisms of miR1273g3p in colorectal cancer remain poorly understood. The expression levels of miR1273g3p in human colorectal cancer LoVo cell lines were detected via reverse transcriptionquantitative polymerase chain reaction (RTqPCR). The target genes of miR1273g3p were predicted by bioinformatics and verified by a luciferase reporter assay, RTqPCR and western blotting. The MTT, woundhealing and Transwell assays were used to examine the biological functions of miR1273g3p in LoVo cells. The potential molecular mechanisms of miR1273g3p on LoVo cell proliferation, migration and invasion was detected by western blotting. The results of the present study demonstrated that miR1273g3p expression was extensively upregulated in LoVo cells compared with the normal colon epithelial NCM460 cell line. Further studies indicated that miR1273g3p inhibitor significantly suppressed LoVo cell proliferation, migration and invasion compared with inhibitor control. Following this, the cannabinoid receptor 1 (CNR1) was identified as a direct target gene of miR1273g3p. Knockdown of CNR1 restored the phenotypes of LoVo cells transfected with miR1273g3p inhibitor. Furthermore, the potential molecular mechanism of miR1273g3p on LoVo cell proliferation, migration and invasion may be mediated by activating the ErbB2 receptor tyrosine kinase 4 (ERBB4)/phosphoinositide3kinase regulatory subunit 3 (PIK3R3)/mechanistic target of rapamycin (mTOR)/S6 kinase 2 (S6K2) signaling pathway. These observations indicated that miR1273g3p promoted the proliferation, migration and invasion of LoVo cells via CNR1, and this may have occurred through activation of the ERBB4/PIK3R3/mTOR/S6K2 signaling pathway, suggesting that miR1273g3p may serve as a novel therapeutic target for the effective treatment of colorectal cancer.
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MEDLINE
Assunto principal:
Fosfatidilinositol 3-Quinases
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Proteínas Quinases S6 Ribossômicas 90-kDa
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MicroRNAs
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Receptor CB1 de Canabinoide
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Serina-Treonina Quinases TOR
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article