Hypoxia/inflammation-induced upregulation of HIF-1 α and C/ EBP β promotes nephroblastoma cell EMT by improving HOXA11-AS transcription

被引：2

作者：

Zhu, Shibo ^{[1
]}

Zhou, Rui ^{[1
]}

Tang, Xiangliang ^{[1
]}

Fu, Wen ^{[1
]}

Jia, Wei ^{[1
]}

机构：

[1] Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Pediat Urol, 9 Jinsui Rd, Guangzhou 510623, Peoples R China

来源：

HELIYON | 2024年 / 10卷 / 06期

关键词：

HOXA11-AS; EMT; Nephroblastoma; HIF-1; alpha; C/EBP beta; TUMOR PROGRESSION; METASTASIS; APOPTOSIS; PROLIFERATION; INFLAMMATION; EXPRESSION; HYPOXIA; TRIALS;

D O I：

10.1016/j.heliyon.2024.e27654

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-1 alpha and C/EBP beta were confirmed to be the transcription factors for HOXA11-AS. Silencing of HIF-1 alpha or C/EBP beta 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 HIF1 alpha or C/EBP beta knockdown. Conclusion: We demonstrated that hypoxia/inflammation-induced upregulation of HIF-1 alpha and C/ EBP beta promoted nephroblastoma EMT by improving HOXA11-AS transcription. HOXA11-AS might be a therapy target for nephroblastoma.

引用

页数：17

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