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非编码 RNA 介导的锌指蛋白 268 的高表达通过促进细胞凋亡和调节免疫细胞浸润来抑制肾透明细胞癌的进展。

Noncoding-RNA mediated high expression of zinc finger protein 268 suppresses clear cell renal cell carcinoma progression by promoting apoptosis and regulating immune cell infiltration.

机构信息

Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, Zha Bei Qu, China.

Department of Neurology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, Zha Bei Qu, China.

出版信息

Bioengineered. 2022 Apr;13(4):10467-10481. doi: 10.1080/21655979.2022.2060787.

Abstract

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant kidney tumors with a poor prognosis. Accumulating evidence proves that zinc finger protein 268 (ZNF268) is associated with tumor progression, but the detailed regulatory functions of ZNF268 in ccRCC require further exploration. Thus, here we aim to characterize the role of ZNF268 in ccRCC. The clinical significance of ZNF268 was evaluated using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Subsequently, tumor-infiltrating immune cells, as well as upstream noncoding RNAs (ncRNAs) related to the tumor-suppressing function of ZNF268, were identified by analyses. The expression of ZNF268 was significantly decreased in ccRCC samples compared with adjacent normal tissues. In addition, ZNF268 expression was negatively correlated with tumor progression and positively correlated with overall and disease-specific survival. TCGA and GTEx databases proved the potential tumor-suppressing function, which was measured both and after ZNF268 over-expression. Overexpression of ZNF268 effectively inhibited the proliferation, migration, invasion and promotied apoptosis of the Caki-1. The level of ZNF268 was positively related to the immune cell infiltration in the tumor. Moreover, we determined that the AC093157.1/miR-27a-3p axis can potentially regulate ZNF268 function in ccRCC. Our work describes a novel ncRNA-mediated ZNF268 function in ccRCC. ZNF268 acts as a tumor suppressor, and it is associated with apoptosis and immune cell infiltration in ccRCC.

摘要

透明细胞肾细胞癌(ccRCC)是最常见的恶性肾肿瘤之一,预后不良。越来越多的证据证明锌指蛋白 268(ZNF268)与肿瘤进展有关,但 ZNF268 在 ccRCC 中的详细调节功能需要进一步探索。因此,我们旨在研究 ZNF268 在 ccRCC 中的作用。使用癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据库评估 ZNF268 的临床意义。随后,通过分析鉴定了与 ZNF268 肿瘤抑制功能相关的肿瘤浸润免疫细胞以及上游非编码 RNA(ncRNA)。与相邻正常组织相比,ccRCC 样本中 ZNF268 的表达明显降低。此外,ZNF268 的表达与肿瘤进展呈负相关,与总生存期和疾病特异性生存期呈正相关。TCGA 和 GTEx 数据库证明了潜在的肿瘤抑制功能,这是通过 ZNF268 过表达后测量的 和 。ZNF268 的过表达有效地抑制了 Caki-1 的增殖、迁移、侵袭和促进凋亡。ZNF268 的水平与肿瘤中免疫细胞浸润呈正相关。此外,我们确定了 AC093157.1/miR-27a-3p 轴可以潜在地调节 ccRCC 中的 ZNF268 功能。我们的工作描述了一种新型 ncRNA 介导的 ZNF268 在 ccRCC 中的功能。ZNF268 作为一种肿瘤抑制因子,与 ccRCC 中的细胞凋亡和免疫细胞浸润有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b89/9161828/664f95936201/KBIE_A_2060787_UF0001_OC.jpg

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