Department of Urology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian Province, China.
Fujian Provincial Reproductive Medicine Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, Fujian Province, China.
Gene. 2024 Jan 30;893:147910. doi: 10.1016/j.gene.2023.147910. Epub 2023 Oct 17.
LINC00887 has been mentioned in several articles regarding its involvement in various cancers like nasopharyngeal carcinoma, lung cancer and glioma. However, the mechanism of LINC00887 in the malignant progression of clear cell renal cell carcinoma (ccRCC) is still unclear. The topic of our study is mainly centered on exploring how LINC00887 exactly affects ccRCC malignant progression.
The bioinformatics method predicted the downstream TF and target genes of LINC00887 by the "LncRNA-transcription factor (TF)-Gene" triplet model. RNA immunoprecipitation, chromatin immunoprecipitation analysis, and Dual-luciferase reporter assay determined the regulatory relationship between LINC00887 and its downstream genes. The LINC00887 expression and its downstream gene expression in ccRCC cells were examined by qRT-PCR and Western blot. The effect of LINC00887-SPI1-CD70 modulation axis on proliferative transfer, cell stemness and T cell chemotaxis of ccRCC cells was examined in cellular and animal experiments.
Our research demonstrated an upregulation of LINC00887 in ccRCC, which facilitated tumor growth and stemness in vivo. In addition, LINC00887 could upregulate the CD70 expression by recruiting transcriptional factor SPI1. The results of in vitro experiments illustrated that the LINC00887-SPI1-CD70 regulatory axis facilitated ccRCC malignant progression by promoting cell stemness and hindering T-cell chemotaxis.
LINC00887, by recruiting SPI1, activated CD70 transcription, thereby propelling malignant progression and cell stemness and suppressing T cell chemotaxis in ccRCC. Based on our findings, we believed that the LINC00887-SPI1-CD70 regulatory axis had the potential to be a critical breakthrough for treating ccRCC.
已有多篇文章提到 LINC00887 参与多种癌症，如鼻咽癌、肺癌和神经胶质瘤。然而，LINC00887 在透明细胞肾细胞癌（ccRCC）恶性进展中的作用机制尚不清楚。我们的研究主题主要集中在探索 LINC00887 如何确切影响 ccRCC 的恶性进展。
采用“LncRNA-转录因子（TF）-基因”三元模型的生物信息学方法预测 LINC00887 的下游 TF 和靶基因。RNA 免疫沉淀、染色质免疫沉淀分析和双荧光素酶报告基因实验确定了 LINC00887 与其下游基因之间的调控关系。通过 qRT-PCR 和 Western blot 检测 ccRCC 细胞中 LINC00887 及其下游基因的表达。在细胞和动物实验中，研究了 LINC00887-SPI1-CD70 调节轴对 ccRCC 细胞增殖转移、细胞干性和 T 细胞趋化性的影响。
我们的研究表明，LINC00887 在 ccRCC 中上调，促进了肿瘤的生长和体内的干性。此外，LINC00887 通过募集转录因子 SPI1 上调 CD70 的表达。体外实验结果表明，LINC00887-SPI1-CD70 调节轴通过促进细胞干性和抑制 T 细胞趋化性，促进 ccRCC 的恶性进展。
LINC00887 通过募集 SPI1 激活 CD70 转录，从而推动 ccRCC 的恶性进展和细胞干性，并抑制 T 细胞趋化性。基于我们的发现，我们认为 LINC00887-SPI1-CD70 调节轴有可能成为治疗 ccRCC 的关键突破。
