Deregulation of RGS17 Expression Promotes Breast Cancer Progression

Deregulation of RGS17 Expression Promotes Breast Cancer Progression
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RGS17 表达失调促进乳腺癌进展。

DOI:
10.7150/jca.11833
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发表时间:
2015-01-01
期刊:
影响因子:
3.9
通讯作者:
Zhao, Ziqin
Zhao, Ziqin
中科院分区:
医学3区
文献类型:
--
作者:
Li, Yuhua;Li, Liliang;Zhao, Ziqin

文献摘要

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目的:RGS17在多种人类肿瘤中均有高水平的表达,并与肿瘤的进展有关。本研究旨在探讨RGS17在乳腺癌中的表达及功能。方法:采用免疫组织化学和免疫印迹方法检测RGS17在乳腺癌组织中的表达。采用定量逆转录聚合酶链式反应检测miR-32的表达水平。Western印迹分析确定RGS17与miR-32之间的关系。结果:RGS17和miR-32在乳腺癌组织和细胞系中的表达水平明显高于正常乳腺组织。虽然未观察到RGS17表达与临床病理特征的潜在关系,但RGS17表达与p63表达显著相关。在细胞中,抑制RGS17的表达会损害细胞的迁移、侵袭和增殖。此外,RGS17被确定为miR-32的直接和功能靶点。在细胞中过表达miR-32可以降低RGS17的表达,抑制细胞的迁移、侵袭和增殖。结论:乳腺癌组织中RGS17的表达上调,促进了细胞的迁移、侵袭和增殖。此外,RGS17被确定为miR-32的目标。我们的结果表明,RGS17可能在乳腺癌的发展过程中发挥重要作用,并可能成为人类乳腺癌治疗的潜在靶点。
Objective: A high level of RGS17 expression is observed in diverse human cancers and correlates with tumor progression. Herein, we aim to investigate its expression and function in breast cancer.Methods: The expression of RGS17 was detected by immunohistochemical analysis and western blot analysis. The level of miR-32 expression was investigated by qRT-PCR. Western blot analysis was used to determine the relationship between RGS17 and miR-32. A series of loss or gain of function assays was performed to measure the effects of RGS17 or miR-32 on tumor migration, invasion, and proliferation.Results: Compared to that in normal breast specimen, the expression of RGS17 had a significantly higher expression level in breast cancer tissues and cell lines. Although the potential relationship of RGS17 expression with clinicopathological features was not observed, there was a significant correlation of RGS17 expression with p63 expression. In cells, inhibition of RGS17 expression impaired cell migration, invasion, and proliferation. Further, RGS17 was identified as a direct and functional target of miR-32. Overexpression of miR-32 in cells could decrease the expression of RGS17 and inhibit cell migration, invasion, and proliferation. In contrast, ectopic expression of RGS17 could attenuate phenotypes caused by miR-32 overexpression.Conclusion: The expression of RGS17 was upregulated in breast cancer, which could enhance cell migration, invasion, and proliferation. Moreover, the RGS17 was identified as a target of miR-32. Our results suggest that RGS17 might play an important role in breast cancer progression and could be a potential target for human breast cancer treatment.