内源性miR103A通过抑制RGS2的表达从而影响乳腺癌的转移

doi:10.3969/j.issn.1009-976X.2021.05.010

摘要/Abstract

摘要： 目的探索内源性miR-103A通过作用于抑癌基因RGS2启动子进而抑制其表达从而影响乳腺癌的转移。方法将从乳腺癌及正常乳腺组织中提取的RNA进行小分子RNA的深度测序检测乳腺癌中小分子RNA的表达,通过生物信息学分析miR103A的目标基因以及其作用位点,用miRNA103A的mimics转染乳腺癌细胞后用QPCR及Western-Blot检测受到影响的肿瘤相关基因,QPCR检测miR103A以及RGS2在乳腺癌及正常癌组织中的差异表达。结果小分子RNA深度测序发现miR103A在乳腺癌及乳腺组织有明显的差异表达且在乳腺癌中高表达,miR103A被发现在伴有淋巴结转移以及HER2+的乳腺癌组织中高表达;生物信息学分析发现miR103A序列能与RGS2的启动子区匹配,且miR103A下调了RGS2 mRNA及蛋白水平;miR103A还上调肿瘤转移相关的MMP9、VGEF、snail、Vimentin的表达,下调了E-cadherin的表达;27例成对临床样本检测发现RGS2在乳腺癌低表达。结论 miR103A通过作用于抑癌基因RGS2的启动子从而下调其表达影响乳腺癌的转移。

关键词: miR103A, 乳腺癌, RGS2, 肿瘤转移

Abstract: Objective To explore the endogenous mir-103A that induces metastasis of breast cancer by downregulating tumor suppressor gene RGS2 through acting on its promoter. Methods Deep-sequencing was practiced to select target small RNAs in breast cancer tissue and normal tissue, and microRNA information retrieval system was used to match the target genes of miR103A. QPCR and Western-Blot were used to detect the expression of RGS2 and possible related genes after the miR103A mimics was transfected into breast cancer cells. The quantitative analysis of RGS2 was performed on cancer and normal tissue from 27 patients. Results Analysis of the deep-sequencing data showed that the major composition of the sequence reads was miRNAs. In addition, the expression of miR103A in breast cancer tissue was significantly higher than that in normal breast tissue. Furthermore, miR103A was found high expressed in HER2+ tumors and in patients with lymph node involved. MiR103A could interact with RGS2 by targeting the promoter region, which leading to a downregulated of RGS2 at both mRNA and protein level. miR103A was also found that could upregulate the expression of MMP9, VGEF, snail, Vimentin but downregulate the expression of E-cadherin in breast cancer cells. Conclusion Endogenous miRNA103A can mediate the cellular negative regulation induced by RGS2, and may lead to the metastasis of tumor.

Key words: miR103A, breast cancer, RGS2, metastasis

中图分类号:

R737.9

陈欣欣, 章乐虹. 内源性miR103A通过抑制RGS2的表达从而影响乳腺癌的转移[J]. 岭南现代临床外科, 2021, 21(05): 541-546.

CHEN Xin-xin, ZHANG Le-hong. Endogenous miR103A promotes metastasis in breast cancer by targeting RGS2 gene[J]. Lingnan Modern Clinics In Surgery, 2021, 21(05): 541-546.

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