Department of Translational Medicine Center, Zhengzhou Central Hospital Affiliated To Zhengzhou University, Zhengzhou, 450007, China.
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
J Cancer Res Clin Oncol. 2020 Aug;146(8):1993-2006. doi: 10.1007/s00432-020-03259-x. Epub 2020 May 22.
Kidney renal clear cell carcinoma (KIRC) is one of the most common lethal cancers in the human urogenital system. As members of the Homeobox (HOX) family, Homeobox-A (HOXA) cluster genes have been reported to be involved in the development of many cancer types. However, the expression and clinical significance of HOXA genes in KIRC remain largely unknown.
In this study, we comprehensively analyzed the mRNA expression and prognostic values of HOXA genes in KIRC using The Cancer Genome Atlas (TCGA) analysis databases online. Colony formation assay, flow cytometry and Western blot were used to detect cell proliferation, apoptosis, cell cycle, and protein level of the indicated gene.
We found that the HOXA genes were differentially expressed in KIRC tissues when compared with normal tissues. The expression of HOXA4 and HOXA13 were significantly up-regulated, while HOXA7 and HOXA11 were down-regulated in KIRC. High mRNA levels of HOXA2, HOXA3 and HOXA13, and low level of HOXA7 predicted poor overall survival (OS) of KIRC patients. High mRNA level of HOXA13 further indicated a poor disease-free survival (DFS) of KIRC patients. Functionally, knockdown of HOXA13 significantly suppressed cell proliferation of KIRC in vitro, increased the protein level of p53 and decreased the protein level of cyclin D1 in KIRC cells. Over-expression of HOXA13 had the opposite effects on KIRC cells.
Collectively, our findings suggest that HOXA13 functions as a novel oncogene in KIRC and may be a potential biomarker for this malignancy.
肾透明细胞癌（KIRC）是人类泌尿生殖系统中最常见的致命癌症之一。作为同源盒（HOX）家族的成员，已报道同源盒-A（HOXA）簇基因参与多种癌症类型的发展。然而，HOXA 基因在 KIRC 中的表达和临床意义在很大程度上仍不清楚。
本研究通过在线分析癌症基因组图谱（TCGA）分析数据库，全面分析了 HOXA 基因在 KIRC 中的 mRNA 表达和预后价值。集落形成实验、流式细胞术和 Western blot 用于检测细胞增殖、凋亡、细胞周期和指示基因的蛋白水平。
我们发现 HOXA 基因在 KIRC 组织中与正常组织相比存在差异表达。HOXA4 和 HOXA13 的表达明显上调，而 HOXA7 和 HOXA11 在 KIRC 中下调。HOXA2、HOXA3 和 HOXA13 的高 mRNA 水平和 HOXA7 的低水平预示着 KIRC 患者的总体生存率（OS）较差。HOXA13 的高 mRNA 水平进一步表明 KIRC 患者的无病生存率（DFS）较差。功能上，HOXA13 的敲低显著抑制了 KIRC 的体外细胞增殖，增加了 KIRC 细胞中 p53 的蛋白水平并降低了细胞周期蛋白 D1 的蛋白水平。HOXA13 的过表达对 KIRC 细胞产生了相反的影响。
综上所述，我们的研究结果表明 HOXA13 作为 KIRC 的一种新型癌基因发挥作用，并且可能是这种恶性肿瘤的潜在生物标志物。
