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Targeting HOXA11‐AS to mitigate prostate cancer via the glycolytic metabolism: In vitro and in vivo
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2024-03-23 , DOI: 10.1111/jcmm.18227
Jiankang Zhang 1 , Sailian Li 2 , Mengyu Zhang 1 , Zhenting Wang 1 , Zengshu Xing 1
Affiliation  

As oncogenes or oncogene suppressors, long‐stranded non‐coding RNAs are essential for the formation and progression of human tumours. However, the mechanisms behind the regulatory role of RNA HOXA11‐AS in prostate cancer (PCa) are unclear. PCa is a common malignant tumour worldwide, and an increasing number of studies have focused on its metabolic profile. Studies have shown that the long non‐coding RNA (lncRNA) HOXA11‐AS is aberrantly expressed in many tumours. However, the role of HOXA11‐AS in PCa is unclear. This work aimed to determine how HOXA11‐AS regulated PCa in vitro and in vivo. We first explored the clinical role of HOXA11‐AS in PCa using bioinformatics methods, including single sample gene set enrichment analysis (ssGSEA), weighted gene co‐expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)‐logistics systematically. In this study, PCa cell lines were selected to assess the PCa regulatory role of HOXA11‐AS overexpression versus silencing in vitro, and tumour xenografts were performed in nude mice to assess tumour suppression by HOXA11‐AS silencing in vivo. HOXA11‐AS expression was significantly correlated with clinicopathological factors, epithelial‐mesenchymal transition (EMT) and glycolysis. Moreover, key genes downstream of HOXA11‐AS exhibited good clinical diagnostic properties for PCa. Furthermore, we studied both in vitro and in vivo effects of HOXA11‐AS expression on PCa. Overexpression of HOXA11‐AS increased PCa cell proliferation, migration and EMT, while silencing HOXA11‐AS had the opposite effect on PCa cells. In addition, multiple metabolites were downregulated by silencing HOXA11‐AS via the glycolytic pathway. HOXA11‐AS silencing significantly inhibited tumour development in vivo. In summary, silencing HOXA11‐AS can inhibit PCa by regulating glucose metabolism and may provide a future guidance for the treatment of PCa.

中文翻译:

靶向 HOXA11-AS 通过糖酵解代谢减轻前列腺癌:体外和体内

作为癌基因或癌基因抑制因子,长链非编码RNA对于人类肿瘤的形成和进展至关重要。然而,RNA HOXA11-AS 在前列腺癌 (PCa) 中的调节作用背后的机制尚不清楚。 PCa是世界范围内常见的恶性肿瘤,越来越多的研究关注其代谢特征。研究表明,长链非编码RNA(lncRNA)HOXA11-AS在许多肿瘤中异常表达。然而,HOXA11-AS 在 PCa 中的作用尚不清楚。这项工作旨在确定 HOXA11-AS 如何在体外和体内调节 PCa。我们首先使用生物信息学方法探讨了 HOXA11-AS 在 PCa 中的临床作用,包括单样本基因集富集分析 (ssGSEA)、加权基因共表达网络分析 (WGCNA) 和最小绝对收缩和选择算子 (LASSO) 逻辑学系统地。在这项研究中,选择PCa细胞系来评估HOXA11-AS过表达与沉默的体外PCa调节作用,并在裸鼠中进行肿瘤异种移植以评估HOXA11-AS沉默在体内的肿瘤抑制作用。 HOXA11-AS 表达与临床病理因素、上皮间质转化(EMT)和糖酵解显着相关。此外,HOXA11-AS下游的关键基因对PCa表现出良好的临床诊断特性。此外,我们研究了 HOXA11-AS 表达对 PCa 的体外和体内影响。 HOXA11-AS 的过度表达会增加 PCa 细胞的增殖、迁移和 EMT,而沉默 HOXA11-AS 对 PCa 细胞具有相反的作用。此外,通过糖酵解途径沉默 HOXA11-AS 可以下调多种代谢物。 HOXA11-AS 沉默显着抑制体内肿瘤的发展。综上所述,沉默HOXA11-AS可以通过调节糖代谢来抑制PCa,可能为未来PCa的治疗提供指导。
更新日期:2024-03-23
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