Zhou Feng-Juan, Meng Sen, Wu Xiao-Feng, Hou Ping-Fu, Li Min-Le, Chu Su-Fang, Bai Jin, Zheng Jun-Nian
The Fourth Clinical College of Nanjing Medical University, Nanjing 211100, Jiangsu Province, China.
Department of Radiotherapy, the Second Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, Jiangsu Province, China.
J Cancer. 2022 Jul 4;13(9):2844-2854. doi: 10.7150/jca.73758. eCollection 2022.
Renal cell carcinoma (RCC) is one of the most prevalent cancers diseases in the worldwide. Long noncoding RNAs (LncRNAs) have been indicated as a mediator acted in tumorigenesis of RCC. LINC00460 has been reported to participate in many kinds of malignancies and promotes cancer progressions. However, the mechanism of LINC00460 on RCC is yet to be investigated. This study aimed to explore the potential function and regulation mechanism of LINC00460 in RCC. We analysed the LINC00460 expression and the prognosis in RCC patients using Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases. LINC00460 level in normal renal cell line and RCC cell lines were examined by qRT-PCR. We study the effects of LINC00460 on proliferation, migration, invasion, apoptosis in RCC cells lines using a series of and experiments. RNA sequencing (RNA-seq) analysis was applied to searching potential LINC00460 related signal pathway in RCC. We identified the significant up-regulated expression of LINC00460 both in RCC tissues and cell. RCC patients with elevated LINC00460 expression have shorter survival. Up-expression of LINC00460 promoted cell proliferation, invasion and migration, meanwhile down-regulation of LINC00460 exerted inhibitory effect on these activities. We crucially identified that LNC00460 promotes development of RCC by influencing the PI3K/AKT pathway. Knockdown of LNC00460 decreased the phosphorylation of AKT and mTOR. The key finding of our study showed that LINC00460 functions as an oncogene in RCC pathogenesis by mediating the PI3K/AKT.
肾细胞癌（RCC）是全球最常见的癌症疾病之一。长链非编码RNA（LncRNAs）已被表明是RCC肿瘤发生过程中的一种介导因子。据报道，LINC00460参与多种恶性肿瘤并促进癌症进展。然而，LINC00460在RCC中的作用机制尚待研究。本研究旨在探讨LINC00460在RCC中的潜在功能和调控机制。我们使用基因表达谱交互式分析（GEPIA）和癌症基因组图谱（TCGA）数据库分析了RCC患者中LINC00460的表达及预后情况。通过qRT-PCR检测正常肾细胞系和RCC细胞系中LINC00460的水平。我们使用一系列实验研究了LINC00460对RCC细胞系增殖、迁移、侵袭和凋亡的影响。应用RNA测序（RNA-seq）分析来寻找RCC中潜在的LINC00460相关信号通路。我们发现LINC00460在RCC组织和细胞中均显著上调表达。LINC00460表达升高的RCC患者生存期较短。LINC00460的上调促进细胞增殖、侵袭和迁移，同时LINC00460的下调对这些活动具有抑制作用。我们关键地确定LNC00460通过影响PI3K/AKT途径促进RCC的发展。敲低LNC00460可降低AKT和mTOR的磷酸化水平。我们研究的关键发现表明，LINC00460通过介导PI3K/AKT在RCC发病机制中发挥癌基因作用。
