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| 題名: | Oxidative Stress Down-Regulates MiR-20b-5p, MiR-106a-5p and E2F1 Expression to Suppress the G1/S Transition of the Cell Cycle in Multipotent Stromal Cells |
| 作者: | Tai, LH (Tai, Lihui)
Huang, CJ (Huang, Chiu-Jung)
Choo, KB (Choo, Kong Bung)
Cheong, SK (Cheong, Soon Keng)
Kamarul, T (Kamarul, Tunku) |
| 貢獻者: | 動科系 |
| 關鍵詞: | oxidative stress
miR-20b-5p & miR-106a-5p
miR-17 family
p21/CDK/E2F1 pathway
E2F1
G1/S transition of cell cycle |
| 日期: | 2020 |
| 上傳時間: | 2020-12-15 10:58:48 (UTC+8) |
| 摘要: | Oxidative stress has been linked to senescence and tumorigenesis via modulation of the cell cycle. Using a hydrogen peroxide (H2O2)-induced oxidative stress-induced premature senescence (OSIPS) model previously reported by our group, this study aimed to investigate the effects of oxidative stress on microRNA (miRNA) expression in relation to the G1-to-S-phase (G1/S) transition of the cell cycle and cell proliferation. On global miRNA analysis of the OSIPS cells, twelve significantly up- or down-regulated miRNAs were identified, the target genes of which are frequently associated with cancers. Four down-regulated miR-17 family miRNAs are predicted to target key pro- and anti-proliferative proteins of the p21/cyclin D-dependent kinase (CDK)/E2F1 pathway to modulate G1/S transition. Two miR-17 miRNAs, miR-20-5p and miR-106-5p, were confirmed to be rapidly and stably down-regulated under oxidative stress. While H2O2 treatment hampered G1/S transition and suppressed DNA synthesis, miR-20b-5p/miR-106a-5p over-expression rescued cells from growth arrest in promoting G1/S transition and DNA synthesis. Direct miR-20b-5p/miR-106a-5p regulation of p21, CCND1 and E2F1 was demonstrated by an inverse expression relationship in miRNA mimic-transfected cells. However, under oxidative stress, E2F1 expression was down-regulated, consistent with hampered G1/S transition and suppressed DNA synthesis and cell proliferation. To explain the observed E2F1 down-regulation under oxidative stress, a scheme is proposed which includes miR-20b-5p/miR-106a-5p-dependent regulation, miRNA-E2F1 autoregulatory feedback and E2F1 response to repair oxidative stress-induced DNA damages. The oxidative stress-modulated expression of miR-17 miRNAs and E2F1 may be used to develop strategies to retard or reverse MSC senescence in culture, or senescence in general. |
| 關聯: | INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 卷冊: 17 期: 4 頁數: 457-470 |
| 顯示於類別: | [動物科學系 ] 期刊論文
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