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miR-122 通过抑制叉头框蛋白 O3 促进透明细胞肾细胞癌的增殖和侵袭。

miR‑122 promotes proliferation and invasion of clear cell renal cell carcinoma by suppressing Forkhead box O3.

机构信息

Department of Urology, Chinese People's Liberation Army, 89th Hospital, Weifang, Shandong 261000, P.R. China.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

出版信息

Int J Oncol. 2019 Feb;54(2):559-571. doi: 10.3892/ijo.2018.4636. Epub 2018 Nov 19.

Abstract

MicroRNAs (miRNAs) serve an important role in renal cancer, but renal cancer miRNA expression data remains inconsistent. Therefore, there is a requirement for integrated analysis of these data. An increasing number of studies demonstrate that miR‑122 is dysregulated in numerous cancer types, including liver, lung and breast cancer, yet its role in clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, an integrated analysis of four ccRCC miRNAs expression datasets was performed and the expression of miR‑122 in the present cohort was validated. The effects of cell proliferation, colony formation, migration and invasion of ccRCC cells in vitro were assayed following transfection with miR‑122 mimics and inhibitor. The target gene of miR‑122 was confirmed using a luciferase reporter assay, and a xenograft mouse model was used to determine the effect of miR‑122 in ccRCC tumorigenicity in vivo. The present results demonstrated that patients with ccRCC with an increased miR‑122 level in tumor tissues had a shortened metastasis‑free survival time as indicated by The Cancer Genome Atlas‑Kidney Renal Clear Cell Carcinoma dataset and the present ccRCC cohort. Overexpression of miR‑122 in 786‑O cells improved cell proliferation, colony formation, migration and invasion, while knockdown of miR‑122 in SN12‑PM6 cells inhibited cell growth, colony formation, migration and invasion. Western blot analysis and luciferase reporter assays were used to identify FOXO3 as a direct target of miR‑122. The present results indicate that miR‑122 serves a tumor‑promoting role by direct targeting FOXO3 in ccRCC.

摘要

微小 RNA(miRNAs)在肾癌中起着重要作用,但肾癌 miRNA 表达数据仍然不一致。因此,需要对这些数据进行综合分析。越来越多的研究表明,miR-122 在许多癌症类型中失调,包括肝癌、肺癌和乳腺癌,但它在透明细胞肾细胞癌(ccRCC)中的作用仍不清楚。在本研究中,对四个 ccRCC miRNAs 表达数据集进行了综合分析,并验证了本队列中 miR-122 的表达。转染 miR-122 模拟物和抑制剂后,检测 ccRCC 细胞在体外的增殖、集落形成、迁移和侵袭能力的影响。利用荧光素酶报告基因检测法证实 miR-122 的靶基因,并利用异种移植小鼠模型在体内确定 miR-122 在 ccRCC 肿瘤发生中的作用。本研究结果表明,根据癌症基因组图谱-肾脏肾透明细胞癌数据集和本 ccRCC 队列,肿瘤组织中 miR-122 水平升高的 ccRCC 患者无转移生存时间缩短。在 786-O 细胞中转染 miR-122 可促进细胞增殖、集落形成、迁移和侵袭,而在 SN12-PM6 细胞中敲低 miR-122 可抑制细胞生长、集落形成、迁移和侵袭。Western blot 分析和荧光素酶报告基因检测法鉴定 FOXO3 为 miR-122 的直接靶基因。本研究结果表明,miR-122 通过直接靶向 ccRCC 中的 FOXO3 发挥促肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/45aa/6317650/c19b9b1944d5/IJO-54-02-0559-g00.jpg

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