miRNA-1260b Promotes Breast Cancer Cell Migration and Invasion by Downregulating CCDC134.

IF 3.8 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2023-01-01 DOI:10.2174/1566523222666220901112314

Zhijian Huang, Shijian Zhen, Liangzi Jin, Jian Chen, Yuanyuan Han, Wen Lei, Fuqing Zhang

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引用次数: 3

Abstract

Background: Breast cancer (BRCA) is the most common type of cancer among women worldwide. MiR-1260b has been widely demonstrated to participate in multiple crucial biological functions of cancer tumorigenesis, but its functional effect and mechanism in human breast cancer have not been fully understood.

Methods: qRT-PCR was used to detect miR-1260b expression in 29 pairs of breast cancer tissues and normal adjacent tissues. Besides, the expression level of miR-1260b in BRCA cells was also further validated by qRT-PCR. miR-1260b played its role in the prognostic process by using Kaplan-Meier curves. In addition, miR-1260b knockdown and target gene CCDC134 overexpression model was constructed in cell line MDA-MB-231. Transwell migration and invasion assay was performed to analyze the effect of miR-1260b and CCDC134 on the biological function of BRCA cells. TargetScan and miRNAWalk were used to find possible target mRNAs. The relationship between CCDC134 and immune cell surface markers was analyzed using TIMER and database and the XIANTAO platform. GSEA analysis was used to identify possible CCDC134-associated molecular mechanisms and pathways.

Results: In the present study, miR-1260b expression was significantly upregulated in human breast cancer tissue and a panel of human breast cancer cell lines, while the secretory protein coiled-coil domain containing 134 (CCDC134) exhibited lower mRNA expression. High expression of miR-1260b was associated with poor overall survival among the patients by KM plot. Knockdown of miR-1260b significantly suppressed breast cancer cell migration and invasion and yielded the opposite result. In addition, overexpression of CCDC134 could inhibit breast cancer migration and invasion, and knockdown yielded the opposite result. There were significant positive correlations of CCDC134 with CD25 (IL2RA), CD80 and CD86. GSEA showed that miR-1260b could function through the MAPK pathway by downregulating CCDC134.

Conclusion: Collectively, these results suggested that miR-1260b might be an oncogene of breast cancer and might promote the migration and invasion of BRCA cells by down-regulating its target gene CCDC134 and activating MAPK signaling pathway as well as inhibiting immune function and causing immune escape in human breast cancer.

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miRNA-1260b通过下调CCDC134促进乳腺癌细胞迁移和侵袭。

背景:乳腺癌(BRCA)是全世界女性中最常见的癌症类型。MiR-1260b已被广泛证实参与肿瘤发生的多种关键生物学功能，但其在人乳腺癌中的功能作用和机制尚不完全清楚。方法:采用qRT-PCR检测29对乳腺癌组织及正常癌旁组织中miR-1260b的表达。此外，我们还通过qRT-PCR进一步验证了miR-1260b在BRCA细胞中的表达水平。Kaplan-Meier曲线显示miR-1260b在预后过程中发挥作用。此外，在MDA-MB-231细胞系中构建miR-1260b敲低和靶基因CCDC134过表达模型。Transwell迁移侵袭实验分析miR-1260b和CCDC134对BRCA细胞生物学功能的影响。TargetScan和miRNAWalk用于寻找可能的靶mrna。利用TIMER、数据库和XIANTAO平台分析CCDC134与免疫细胞表面标志物的关系。采用GSEA分析确定可能与ccdc134相关的分子机制和途径。结果:在本研究中，miR-1260b在人乳腺癌组织和一组人乳腺癌细胞系中表达显著上调，而含有134的分泌蛋白线圈结构域(CCDC134) mRNA表达较低。KM图显示，miR-1260b的高表达与患者的总生存期较差相关。miR-1260b敲低可显著抑制乳腺癌细胞的迁移和侵袭，结果相反。此外，CCDC134过表达可以抑制乳腺癌的迁移和侵袭，而敲低则相反。CCDC134与CD25 (IL2RA)、CD80、CD86呈显著正相关。GSEA显示miR-1260b可以通过下调CCDC134通过MAPK途径发挥作用。结论:综上所述，这些结果提示miR-1260b可能是乳腺癌的致癌基因，在人乳腺癌中，miR-1260b可能通过下调其靶基因CCDC134，激活MAPK信号通路，抑制免疫功能，引起免疫逃逸，从而促进BRCA细胞的迁移和侵袭。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.