Wang Siyuan, Yang Xiaorong, Xie Wenjie, Fu Shengqiang, Chen Qiang, Li Zhilong, Zhang Zhicheng, Sun Ting, Gong Binbin, Ma Ming
Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Front Oncol. 2021 Oct 14;11:718532. doi: 10.3389/fonc.2021.718532. eCollection 2021.
Long noncoding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Gastric adenocarcinoma-associated, positive CD44 regulator, long intergenic noncoding RNA (GAPLINC) is a recently identified lncRNA that can actively participate in the tumorigenesis of various cancers. Here, we investigated the functional roles and mechanism of GAPLINC in renal cell carcinoma (RCC) development.
Differentially expressed lncRNAs between RCC tissues and normal kidney tissues were detected by using a microarray technique. RNA sequencing was applied to explore the mRNA expression profile changes after GAPLINC silencing. After gain- and loss-of-function approaches were implemented, the effect of GAPLINC on RCC and was assessed by cell proliferation and migration assays. Moreover, rescue experiments and luciferase reporter assays were used to study the interactions between GAPLINC, miR-135b-5p and CSF1.
GAPLINC was significantly upregulated in RCC tissues and cell lines and was associated with a poor prognosis in RCC patients. Knockdown of GAPLINC repressed RCC growth and , while overexpression of GAPLINC exhibited the opposite effect. Mechanistically, we found that GAPLINC upregulates oncogene CSF1 expression by acting as a sponge of miR-135b-5p.
Taken together, our results suggest that GAPLINC is a novel prognostic marker and molecular therapeutic target for RCC.
长链非编码RNA(lncRNAs)与癌症的发生和发展密切相关。胃腺癌相关的、阳性CD44调节因子、长链基因间非编码RNA(GAPLINC)是最近发现的一种lncRNA,可积极参与各种癌症的肿瘤发生。在此,我们研究了GAPLINC在肾细胞癌(RCC)发展中的功能作用和机制。
使用微阵列技术检测RCC组织和正常肾组织之间差异表达的lncRNAs。应用RNA测序来探索GAPLINC沉默后mRNA表达谱的变化。在实施功能获得和功能丧失方法后,通过细胞增殖和迁移试验评估GAPLINC对RCC的影响。此外,采用挽救实验和荧光素酶报告基因试验来研究GAPLINC、miR-135b-5p和CSF1之间的相互作用。
GAPLINC在RCC组织和细胞系中显著上调,并且与RCC患者的不良预后相关。敲低GAPLINC可抑制RCC生长,而GAPLINC的过表达则表现出相反的效果。机制上,我们发现GAPLINC通过充当miR-135b-5p的海绵来上调癌基因CSF1的表达。
综上所述,我们的结果表明GAPLINC是RCC的一种新型预后标志物和分子治疗靶点。