Prolonged survival of renal cancer patients is concomitant with a higher regucalcin gene expression in tumor tissues: Overexpression of regucalcin suppresses the growth of human renal cell carcinoma cells in vitro.
Prolonged survival of renal cancer patients is concomitant with a higher regucalcin gene expression in tumor tissues: Overexpression of regucalcin suppresses the growth of human renal cell carcinoma cells in vitro.
复制标题
DOI：
10.3892/ijo.2018.4611
复制
发表时间：
2018-10
影响因子：
5.2
通讯作者：
M. Yamaguchi;S. Osuka;O. Hankinson;T. Murata
中科院分区：
文献类型：
--
作者：
M. Yamaguchi;S. Osuka;O. Hankinson;T. Murata
肾细胞癌（RCC）是一种在肾小管中发现的癌症，是10种最常见的人类癌症之一。Regucalcin作为转录活性的调节剂发挥潜在的作用，并且其下调的表达或活性可能有助于促进人类癌症。在这项研究中，我们调查regucalcin在人类肾癌的参与。通过基因表达综合数据库（GEO）（GSE 36895）获得的透明细胞RCC患者的肾皮质组织的23个正常和29个肿瘤样品中的Regucalcin表达进行比较。Regucalcin在肿瘤组织中表达下调。透明细胞肾细胞癌患者的长期生存被证明与TCGA数据集中更高的regucalcin基因表达相关。regucalcin过表达抑制体外培养的人透明细胞RCC A498细胞的殖民地形成、增殖和死亡。机制上，regucalcin的过表达通过抑制多种信号组分（包括Ras、PI 3激酶、Akt和丝裂原活化蛋白（MAP）激酶）诱导A498细胞的G1和G2/M期细胞周期停滞。重要的是，regucalcin的过度表达导致肿瘤抑制因子p53、Rb和细胞周期抑制因子p21的水平升高。regucalcin过表达抑制了转录因子c-fos、c-jun、核因子-κB p65、β-catenin和信号转导和转录激活因子3的水平。总体而言，本研究的结果表明regucalcin在人RCC的促进中起抑制作用。因此，通过基因递送系统过表达regucalcin可能被证明是RCC的一种新治疗策略。
Renal cell carcinoma (RCC), which is a type of cancer found in the kidney tubule, is among the 10 most frequently occurring human cancers. Regucalcin plays a potential role as a regulator of transcriptional activity, and its downregulated expression or activity may contribute to the promotion of human cancers. In this study, we investigated the involvement of regucalcin in human RCC. Regucalcin expression was compared in 23 normal and 29 tumor samples of kidney cortex tissues of patients with clear cell RCC obtained through the Gene Expression Omnibus (GEO) database (GSE36895). Regucalcin expression was downregulated in the tumor tissues. The prolonged survival of patients with clear cell RCC was demonstrated to be associated with a higher regucalcin gene expression in the TCGA dataset. The overexpression of regucalcin suppressed the colony formation, proliferation and the death of human clear cell RCC A498 cells in vitro. Mechanistically, the overexpression of regucalcin induced the G1 and G2/M phase cell cycle arrest of A498 cells through the suppression of multiple signaling components, including Ras, PI3 kinase, Akt and mitogen‑activated protein (MAP) kinase. Importantly, the overexpression of regucalcin led to an elevation in the levels of the tumor suppressors, p53, Rb and the cell cycle inhibitor, p21. The levels of the transcription factors, c‑fos, c‑jun, nuclear factor‑κB p65, β‑catenin and signal transducer and activator of transcription 3, were suppressed by regucalcin overexpression. On the whole, the findings of this study suggest that regucalcin plays a suppressive role in the promotion of human RCC. The overexpression of regucalcin by gene delivery systems may thus prove to be a novel therapeutic strategy for RCC.