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微小RNA-1275通过上调胰岛素样生长因子-1受体(IGF-1R)和趋化因子受体7(CCR7)促进头颈部鳞状细胞癌的细胞迁移、侵袭和增殖。

MiR-1275 promotes cell migration, invasion and proliferation in squamous cell carcinoma of head and neck via up-regulating IGF-1R and CCR7.

作者信息

Liu Min-Da, Wu Hong, Wang Song, Pang Pai, Jin Shan, Sun Chang-Fu, Liu Fa-Yu

机构信息

Department of Oromaxillofacial-Head and Neck, Oral Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, PR China.

Department of Oromaxillofacial-Head and Neck, Oral Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning 110002, PR China.

出版信息

Gene. 2018 Mar 10;646:1-7. doi: 10.1016/j.gene.2017.12.049. Epub 2017 Dec 24.

Abstract

PURPOSE

miRNAs can play vital role in migration, invasion and proliferation in Squamous cell carcinoma of head and neck (SCCHN). In our study, we attempted to validate the expression and function of miR-1275 in SCCHN, and we also identified the mechanism by which miR-1275 affects migration, invasion and proliferation of SCCHN.

METHODS

Real-time polymerase chain reaction (RT-PCR) was employed to evaluate the expression of miR-1275 in both SCCHN tissues and cell lines. The role of miR-1275 in SCCHN cells was verified by cell function experiments upon transfection with miR-1275 mimics and inhibitor. Western blot analysis was employed to test the target gene expression of miR-1275. Survival analysis was made with the information of SCCHN patients expressed miR-1275 from The Cancer Genome Atlas (TCGA) database.

RESULTS

miR-1275 expression was up-regulated in SCCHN tissues and advanced metastatic SCCHN cells. Increasing miR-1275 expression in SCCHN could promote cell migration, invasion and proliferation probably by upregulating Insulin-like growth factor 1 receptor (IGF-1R) and C-C chemokine receptor type 7(CCR7) protein levels, whereas inhibition of miR-1275 could lead the opposite effects, although others have already demonstrated that IGF-1R is a direct target of miR-1275. Survival analysis suggested that patients with lower miR-1275 expression may have a better outcome.

CONCLUSIONS

Herein we report for the first time that miR-1275 could act as a tumor-promoter in SCCHN possibly by regulating its target gene via novel miRNA mechanisms. MiR-1275 plays an important role in promoting SCCHN progression. The miR-1275 may be a potential therapeutic target for SCCHN treatment in the future.

摘要

目的

微小RNA(miRNA)在头颈部鳞状细胞癌(SCCHN)的迁移、侵袭和增殖中发挥着至关重要的作用。在本研究中,我们试图验证miR-1275在SCCHN中的表达及功能,并确定miR-1275影响SCCHN迁移、侵袭和增殖的机制。

方法

采用实时聚合酶链反应(RT-PCR)评估miR-1275在SCCHN组织和细胞系中的表达。通过用miR-1275模拟物和抑制剂转染后的细胞功能实验,验证miR-1275在SCCHN细胞中的作用。采用蛋白质免疫印迹分析检测miR-1275的靶基因表达。利用癌症基因组图谱(TCGA)数据库中SCCHN患者的miR-1275表达信息进行生存分析。

结果

miR-1275在SCCHN组织和晚期转移性SCCHN细胞中表达上调。增加SCCHN中miR-1275的表达可能通过上调胰岛素样生长因子1受体(IGF-1R)和C-C趋化因子受体7型(CCR7)蛋白水平促进细胞迁移、侵袭和增殖,而抑制miR-1275则会产生相反的效果,尽管其他人已经证明IGF-1R是miR-1275的直接靶标。生存分析表明,miR-1275表达较低的患者可能预后较好。

结论

在此我们首次报道,miR-1275可能通过新的miRNA机制调节其靶基因,从而在SCCHN中充当肿瘤促进因子。miR-1275在促进SCCHN进展中起重要作用。miR-1275可能是未来SCCHN治疗的潜在靶点。

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