miRNA-27b-3p/TPX2轴调节透明细胞肾细胞癌细胞的增殖、侵袭和迁移。

IF 1.5 4区 医学 Q4 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Nana Liu, Yicheng Jiang, Shiyuan Chen, Fang Pan, Yao Tang, Xingping Tan
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引用次数: 0

摘要

有多种癌症细胞可能与TPX2的存在有关。然而,关于其在透明细胞肾细胞癌(ccRCC)的发展和维持中的作用,还没有很多证据。在我们的研究中,进行了生物信息学分析,以获得ccRCC中差异表达的mRNA和miR NA。生存曲线预测了TPX2表达与患者生存率的相关性。通过数据库预测TPX2的上游调控miRNA为miRNA-27b-3p,双荧光素酶测定验证了靶向关系。采用qRT-PCR和Western blot方法检测TPX2 mRNA和蛋白在ccRCC细胞中的表达。通过CCK-8、集落形成、伤口愈合、Transwell和流式细胞术检测增殖、侵袭、迁移和细胞周期。结果显示,TPX2在ccRCC中表现出非常高的表达,并且TPX2表达较高的患者的相对生存期较短。在ccRCC中发现miRNA-27b-3p的低表达。在ccRCC细胞中敲除TPX2或强制表达miRNA-27b-3p可抑制细胞增殖、迁移、侵袭,并在G0/G1期阻止细胞分裂。双荧光素酶报告基因提示miRNA-27b-3p靶向TPX2以抑制其表达。拯救实验表明,miRNA-27b-3p/TPX2轴影响ccRCC细胞的生物学功能。miRNA-27b-3p和TPX2的同时过表达抑制了TPX2对ccRCC细胞生长的促进作用。研究结果揭示了参与ccRCC进展的新的调控机制,希望它能为以后发现ccRCC的新治疗靶点提供线索。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
miRNA-27b-3p/TPX2 Axis Regulates Clear Cell Renal Cell Carcinoma Cell Proliferation, Invasion and Migration.

There is a wide variety of cancer cells that can be linked to the presence of TPX2. However, there is not a lot of evidence regarding its role in the development and maintenance of clear cell renal cell carcinoma (ccRCC). In our study, bioinformatics analysis was performed to obtain differentially expressed mRNAs and miR-NAs in ccRCC. Survival curves predicted correlation of TPX2 expression with patient survival. The upstream regulatory miRNA of TPX2 was predicted to be miRNA-27b-3p through database, and dual luciferase assay verified the targeted relationship. qRT-PCR and Western blot were employed for examination of TPX2 mRNA and protein expression in ccRCC cells. Proliferation, invasion, migration and cell cycle were detected by CCK-8, colony formation, wound healing, Transwell, and flow cytometry assays. The results showed that TPX2 showed very high expression in ccRCC, and patients with higher TPX2 expression had shorter relative survival. Low miRNA-27b-3p expression was found in ccRCC. Knockdown of TPX2 or forced expression of miRNA-27b-3p in ccRCC cells inhibited cell proliferation, migration, invasion, and arrested cell division in G0/G1 phase. Dual luciferase reporter presented that miRNA-27b-3p targeted TPX2 to inhibit its expression. Rescue experiments demonstrated that the miRNA-27b-3p/ TPX2 axis affected the biological functions of ccRCC cells. Concurrent overexpression of miRNA-27b-3p and TPX2 inhibited the facilitating effect of TPX2 on ccRCC cell growth. The results revealed novel regulatory mechanisms involved in ccRCC progression, hoping that it may spark an insight for later discovery about the new therapeutic targets for ccRCC.

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来源期刊
Critical Reviews in Eukaryotic Gene Expression
Critical Reviews in Eukaryotic Gene Expression 生物-生物工程与应用微生物
CiteScore
2.70
自引率
0.00%
发文量
67
审稿时长
1 months
期刊介绍: Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource. Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.
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