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miR-143 通过抑制 ABL2 抑制肾癌细胞的转移潜能。

miR-143 inhibits renal cell carcinoma cells metastatic potential by suppressing ABL2.

机构信息

Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.

Department of Urology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

出版信息

Kaohsiung J Med Sci. 2020 Aug;36(8):592-598. doi: 10.1002/kjm2.12207. Epub 2020 Mar 20.

Abstract

Although micro RNA (miRNA) expression profiles are widely investigated in renal cell carcinoma (RCC), their potential roles for affecting RCC initiation and progression remain largely unknown. Here, we examined the aberrant expression profiles of miRNAs inhuman metastatic RCC tissues based on Gene Expression Omnibus (GSE37989). We further validated them iRNAs expression data in the largest clinical dataset: The Cancer Genome Atlas (TCGA). And cell adhesion and migration abilities and epithelial me senchymal transition (EMT) related proteins were assessed in both normal and tumor RCC cell lines. We suggest that hsa-miR-143 is a potential tumor suppressor in RCC as its down regulation positively correlated with adverse prognosis. Biologically, cell adhesion, migration, and EMT were dramatically inhibited by miR-143. Mechanistically, we found that miR-143 targets ABL proto-oncogene 2 (ABL2), which was also found to be an indicator for poor survival in TCGA database. Our results have important implications in understanding functions of miRNAs in metastatic RCC and will provide a basis for further clinical application.

摘要

虽然 micro RNA (miRNA) 表达谱在肾细胞癌 (RCC) 中得到了广泛的研究,但它们在影响 RCC 发生和发展方面的潜在作用在很大程度上仍然未知。在这里,我们基于基因表达综合数据库 (GEO) 检查了人转移性 RCC 组织中 miRNA 的异常表达谱。我们进一步在最大的临床数据集——癌症基因组图谱 (TCGA) 中验证了这些 miRNA 的表达数据。然后在正常和肿瘤 RCC 细胞系中评估了细胞黏附和迁移能力以及上皮间质转化 (EMT) 相关蛋白。我们认为 hsa-miR-143 是 RCC 中的一种潜在肿瘤抑制因子,因为它的下调与不良预后呈正相关。从生物学角度来看,miR-143 显著抑制了细胞黏附、迁移和 EMT。从机制上讲,我们发现 miR-143 靶向 ABL 原癌基因 2 (ABL2),在 TCGA 数据库中,ABL2 也是一个预后不良的指标。我们的研究结果对理解 miRNA 在转移性 RCC 中的功能具有重要意义,并将为进一步的临床应用提供基础。

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