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肿瘤抑制因子miR-33b-5p调节细胞功能,并作为肾细胞癌的预后生物标志物。

Tumor suppressor miR-33b-5p regulates cellular function and acts a prognostic biomarker in RCC.

作者信息

Huang Guocheng, Lai Yulin, Pan Xiang, Zhou Liang, Quan Jing, Zhao Liwen, Li Zuwei, Lin Canbin, Wang Jingyao, Li Hang, Yuan Haichao, Yang Yu, Lai Yongqing, Ni Liangchao

机构信息

Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital Shenzhen 518036, Guangdong, P. R. China.

Shantou University Medical College Shantou 515041, Guangdong, P. R. China.

出版信息

Am J Transl Res. 2020 Jul 15;12(7):3346-3360. eCollection 2020.

Abstract

BACKGROUND

Renal cell carcinoma (RCC) is a renal parenchyma neoplasm with a 30% recurrence rate even when treated properly. MicroRNAs are noncoding small RNAs that are involved in cellular communication and may participate in cancer development. This study aimed to explore the relationship between miR-33b-5p expression and RCC progression and prognosis.

METHOD

RT-qPCR, CCK-8 assay, wound scratch assay, transwell assay and flow cytometry assay were used to evaluate the expression and function of miR-33b-5p in RCC. Additionally, RCC samples and survival data from The Cancer Genome Atlas were used to analyze the prognostic functions of miR-33b-5p.

RESULTS

miR-33b-5p expression in RCC tissues and cell lines (786-O, ACHN) were found to be significantly downregulated, compared with normal tissues and cell lines (P<0.001). The miR-33b-5p mimic transfected cells showed a slower proliferation rate (P<0.01), while its invasion ability decreased by 38.16% (786-O, P<0.001) and 49.19% (ACHN, P<0.05), compared with the negative control (NC). The migration ability of both RCC lines were found to be as follows: miR-33b-5p inhibitor > NC or NC inhibitor > miR-33b-5p mimic. Additionally, TCGA and RCC samples reveal that low miR-33b-5p expression is related to poor survival outcomes (univariate analysis, P=0.029; multivariate analysis, P=0.024; Kaplan-Meier survival curves, P=0.014). Target genes prediction suggests that miR-33b-5p performs its tumor-suppressive effects and prognostic role through targeting TBX15, SLC12A5, and PTGFRN.

CONCLUSIONS

miR-33b-5p may function as a tumor-suppressive regulator and prognostic biomarker in RCC.

摘要

背景

肾细胞癌(RCC)是一种肾实质肿瘤,即使经过适当治疗,其复发率仍为30%。微小RNA是参与细胞通讯的非编码小RNA,可能参与癌症发展。本研究旨在探讨miR-33b-5p表达与RCC进展及预后之间的关系。

方法

采用RT-qPCR、CCK-8检测、伤口划痕试验、Transwell试验和流式细胞术检测评估miR-33b-5p在RCC中的表达和功能。此外,使用来自癌症基因组图谱的RCC样本和生存数据来分析miR-33b-5p的预后功能。

结果

与正常组织和细胞系相比,RCC组织和细胞系(786-O、ACHN)中的miR-33b-5p表达显著下调(P<0.001)。与阴性对照(NC)相比,转染miR-33b-5p模拟物的细胞增殖速率较慢(P<0.01),其侵袭能力分别降低了38.16%(786-O,P<0.001)和49.19%(ACHN,P<0.05)。两种RCC细胞系的迁移能力如下:miR-33b-5p抑制剂>NC或NC抑制剂>miR-33b-5p模拟物。此外,TCGA和RCC样本显示,低miR-33b-5p表达与不良生存结果相关(单因素分析,P=0.029;多因素分析,P=0.024;Kaplan-Meier生存曲线,P=0.014)。靶基因预测表明,miR-33b-5p通过靶向TBX15、SLC12A5和PTGFRN发挥其肿瘤抑制作用和预后作用。

结论

miR-33b-5p可能作为RCC中的肿瘤抑制调节因子和预后生物标志物发挥作用。

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