Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion.
Loss of miR-133a expression associated with poor survival of breast cancer and restoration of miR-133a expression inhibited breast cancer cell growth and invasion.
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miR-133a 表达缺失与乳腺癌存活率低相关，而 miR-133a 表达恢复则抑制乳腺癌细胞生长和侵袭
DOI：
10.1186/1471-2407-12-51
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发表时间：
2012-02-01
期刊：
影响因子：
3.8
通讯作者：
Wu Q
中科院分区：
文献类型：
--
作者：
Wu ZS;Wang CQ;Xiang R;Liu X;Ye S;Yang XQ;Zhang GH;Xu XC;Zhu T;Wu Q
微小RNA（miRNAs）是内源性寡核苷酸RNA，在乳腺肿瘤发生和肿瘤进展中起重要作用。对其表达的检测以及对其功能的研究可能会发现乳腺癌的新型生物标志物。
原位杂交用于检测26例良性、34例癌旁正常和90例癌性组织的福尔马林固定石蜡包埋的乳腺手术标本中miR - 133a的表达。实时定量逆转录聚合酶链反应（qRT - PCR）用于评估6种乳腺细胞系以及10例良性和18例癌性新鲜乳腺组织标本中miR - 133a的水平。细胞活力、迁移和侵袭实验分别用于确定miR - 133a在调节乳腺癌细胞生长、迁移和侵袭中的作用。荧光素酶实验用于评估miR - 133a与FSCN1基因的结合。
从正常乳腺组织到良性再到癌性乳腺组织，miR - 133a的表达降低。在乳腺癌细胞系中，miR - 133a的表达也较低。miR - 133a表达降低与乳腺癌患者的淋巴结转移、临床分期高以及无复发生存期较短有关。此外，与阴性对照相比，miR - 133a寡核苷酸转染略微抑制乳腺癌细胞的生长，但显著降低其迁移和侵袭能力，而miR - 133a表达的敲低则诱导乳腺癌细胞迁移和侵袭。此外，我们使用一种在线生物信息学工具在成束蛋白1（FSCN1）基因的3' - 非翻译区（UTR）中确定了一个假定的miR - 133a结合位点。我们发现miR - 133a转染显著降低了FSCN1 mRNA和蛋白质的表达。荧光素酶报告基因实验证实FSCN1是miR - 133a的直接靶基因。
miR - 133a在乳腺癌组织中表达缺失，这种缺失与乳腺癌患者的淋巴结转移、临床分期高以及无复发生存期较短有关。在功能上，miR - 133a能够抑制肿瘤细胞的侵袭和迁移，并靶向FSCN1的表达。未来的研究将验证miR - 133a表达的检测是否可作为乳腺癌进展和患者预后的新型生物标志物。
BackgroundmiRNAs, endogenous oligonucleotide RNAs, play an important role in mammary gland carcinogenesis and tumor progression. Detection of their expression and investigation of their functions could lead to discovery of novel biomarkers for breast cancer.MethodsIn situhybridization was used to detect miR-133a expression in formalin-fixed paraffin-embedded breast surgical specimens from 26 benign, 34 pericancerously normal and 90 cancerous tissues. qRT-PCR was performed to assess miR-133a levels in 6 breast cell lines and 10 benign and 18 cancerous fresh breast tissue specimens. Cell viability, migration, and invasion assays were used to determine the role of miR-133a in regulation of breast cancer cell growth, migration, and invasion, respectively. Luciferase assay was performed to assess miR-133a binding to FSCN1 gene.ResultsExpression of miR-133a was reduced from normal through benign to cancerous breast tissues. Expression of miR-133a was also low in breast cancer cell lines. The reduced miR-133a expression was associated with lymph nodes metastasis, high clinical stages, and shorter relapse-free survivals of patients with breast cancer. Furthermore, transfection of miR-133a oligonucleotides slightly inhibited growth but significantly decreased migration and invasion capacity of breast cancer cells, compared with negative controls, whereas knockdown of miR-133a expression induced breast cancer cell migration and invasion. In addition, we identified a putative miR-133a binding site in the 3'-untranslated region (UTR) of Fascin1 (FSCN1) gene using an online bioinformatical tool. We found that miR-133a transfection significantly reduced expression of FSCN1 mRNA and protein. The luciferase reporter assay confirmed that FSCN1 was the direct target gene of miR-133a.ConclusionsmiR-133a expression was lost in breast cancer tissues, loss of which was associated with lymph nodes metastasis, high clinical stages and shorter relapse-free survivals of patients with breast cancer. Functionally, miR-133a can suppress tumor cell invasion and migration and targeted the expression of FSCN1. Future study will verify whether detection of miR-133a expression can served as a novel biomarker for breast cancer progression and patient prognosis.
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影响因子：
8.8
作者：
通讯作者：
--
影响因子：
21.3
作者：
Ma, Li;Young, Jennifer;Prabhala, Harsha;Pan, Elizabeth;Mestdagh, Pieter;Muth, Daniel;Teruya-Feldstein, Julie;Reinhardt, Ferenc;Onder, Tamer T.;Valastyan, Scott;Westermann, Frank;Speleman, Frank;Vandesompele, Jo;Weinberg, Robert A.
通讯作者：
Weinberg, Robert A.
DOI：
10.1038/modpathol.2009.161
发表时间：
2010-03
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Iorio, MV;Ferracin, M;Croce, CM
通讯作者：
Croce, CM
DOI：
10.1073/pnas.0602266103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Costinean, S;Zanesi, N;Croce, CM
通讯作者：
Croce, CM