論文 - 詳細
| RRC ID | 78629 |
|---|---|
| 著者 | Zhu S, Zhou R, Tang X, Fu W, Jia W. |
| タイトル | Hypoxia/inflammation-induced upregulation of HIF-1α and C/EBPβ promotes nephroblastoma cell EMT by improving HOXA11-AS transcription. |
| ジャーナル | Heliyon |
| Abstract |
BACKGROUND:Homeobox (HOX) A11 antisense RNA (HOXA11-AS) has been identified as a cancer promoting lncRNA and is overexpressed in nephroblastoma. However, how HOXA11-AS is regulated in a hypoxic inflammatory environment has not been studied. METHODS:In this study, gene expression and epithelial-mesenchymal transition (EMT) ability were detected in the nephroblastoma cell line WiT49 under conditions of hypoxia and inflammation. Next, HOXA11-AS transcription factors were predicted by datasets and subsequently confirmed by CHIP-QPCR, EMSA, and dual-luciferase reporter assays. Moreover, the regulatory relationships of HOXA11-AS and its transcription factors were further confirmed by rescue experiments. RESULTS:Our results showed that a hypoxic microenvironment promoted HOXA11-AS expression and nephroblastoma progression, induced EMT, and activated the Wnt signaling pathway. Combined hypoxia and inflammation had a more substantial effect on nephroblastoma than either hypoxia or inflammation alone. HIF-1α and C/EBPβ were confirmed to be the transcription factors for HOXA11-AS. Silencing of HIF-1α or C/EBPβ downregulated HOXA11-AS expression and suppressed EMT and the Wnt signaling pathway in nephroblastoma cells exposed to a hypoxic or inflammatory microenvironment. HOXA11-AS overexpression partly reversed the effect of HIF-1α or C/EBPβ knockdown. CONCLUSION:We demonstrated that hypoxia/inflammation-induced upregulation of HIF-1α and C/EBPβ promoted nephroblastoma EMT by improving HOXA11-AS transcription. HOXA11-AS might be a therapy target for nephroblastoma. |
| 巻・号 | 10(6) |
| ページ | e27654 |
| 公開日 | 2024-3-30 |
| DOI | 10.1016/j.heliyon.2024.e27654 |
| PII | S2405-8440(24)03685-5 |
| PMID | 38524550 |
| PMC | PMC10958367 |
| リソース情報 | |
| ヒト・動物細胞 | HFWT(RCB0665) |