Lentivirus-mediated RIG-I knockdown relieves cell proliferation inhibition, cell cycle arrest and apoptosis in ATRA-induced NB4 cells via the AKT-FOXO3A signaling pathway in vitro
| Autor: | Hua Pang, Wei‑Dong Su, Yu‑Ling Si, Xin‑Chao Wang, Ya‑Bin Cui, Li‑Jun Qiu, Lei Chen |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Cell cycle checkpoint proliferation viruses Cell Tretinoin Biology Biochemistry 03 medical and health sciences Leukemia Promyelocytic Acute Cell Line Tumor Genetics medicine Humans short hairpin RNA Receptors Immunologic Molecular Biology Protein kinase B Cell Proliferation Gene knockdown phosphoinositide-3 kinase/Akt Gene Expression Regulation Leukemic Cell growth Forkhead Box Protein O3 Lentivirus Forkhead box O3A apoptosis virus diseases Cell Cycle Checkpoints Articles retinoic acid inducible gene I Cell cycle Molecular biology Cell biology 030104 developmental biology medicine.anatomical_structure Oncology Gene Knockdown Techniques DEAD Box Protein 58 Molecular Medicine cell cycle Signal transduction Proto-Oncogene Proteins c-akt A431 cells Signal Transduction |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2017.6858 |
| Popis: | Retinoic acid inducible gene I (RIG-I) is upregulated during all-trans retinoic acid (ATRA)-induced terminal granulocytic differentiation of NB4 acute promyelocytic leukemia (APL) cells. However, the function and mechanism of RIG-I in NB4 cells remains to be fully elucidated. In the present study, lentivirus-mediated RIG-I-knockdown was used to investigate the proliferation, cell cycle and apoptotic processes of ATRA-induced NB4 cells in vitro using an MTT assay and flow cytometry, respectively. The roles of RIG-I and the AKT-FOXO3A signaling pathway were investigated using western blot analysis. The results showed that the ATRA-induced expression of RIG-I was specifically and effectively knocked down at the mRNA and protein levels by lentivirus mediated RIG-I short hairpin RNA. In addition, silencing of RIG-I reduced the ATRA-induced inhibition of NB4 cell proliferation, cell cycle arrest and apoptosis. Further investigations indicated that with ATRA-induced expression of RIG-I, levels of phosphorylated (p)AKT-Thr308 and pForkhead Box (FOX) O3A-Thr32 were decreased, the expression levels of cell cycle arrest protein p27 and the apoptotic protein, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), directly transcribed by FOXO3A were increased. By contrast, following the knockdown of ATRA-induced expression of RIG-I, the levels of pAKT-Thr308 and pFOXO3A-Thr32 were increased, and the protein expression levels of p27 and TRAIL were decreased. Taken together, these results showed that the knockdown of RIG-I reduced the inhibition of cell proliferation, cell cycle arrest and apoptosis in the ATRA-induced NB4 cells via the AKT-FOXO3A signaling pathway. |
| Databáze: | OpenAIRE |
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