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微小RNA-145通过靶向基质金属蛋白酶11和Rab GTP酶家族27a在三阴性乳腺癌中发挥肿瘤抑制作用。

MicroRNA-145 functions as a tumor suppressor by targeting matrix metalloproteinase 11 and Rab GTPase family 27a in triple-negative breast cancer.

作者信息

Tang L, Wei D, Yan F

机构信息

Department of Clinical Laboratory, Nanjing Medical University Cancer Hospital, Nanjing, PR China.

Department of Surgery, Nanjing Medical University Cancer Hospital, Nanjing, PR China.

出版信息

Cancer Gene Ther. 2016 Aug;23(8):258-65. doi: 10.1038/cgt.2016.27. Epub 2016 Jul 1.

Abstract

Although increasing evidence has documented that microRNA-145 (miR-145) acts as a tumor suppressor in breast cancer, its exact role in triple-negative breast cancer (TNBC) remains poorly defined. In this study, the expression of miR-145 in human TNBC cells and samples from 30 patients was analyzed by stem-loop real-time PCR. We found that miR-145 was significantly downregulated in TNBC tissues and cells. Upregulating miR-145 in HCC1937 cells dramatically suppressed cell proliferation and induced G1-phase arrest, whereas MDA-MB-231 cells did not show growth inhibition. MiR-145 exhibited an inhibitory role in cell invasion through the post-transcriptional regulation of the novel targets MMP11 and Rab27a in TNBC cells. Additionally, miR-145 silencing could be reversed by 5-aza-2'-deoxycytidine (DAC). These results demonstrated that miR-145 has an inhibitory role in TNBC malignancy by targeting MMP11 and Rab27a, which might be potential therapeutic and diagnostic targets for TNBC.

摘要

尽管越来越多的证据表明,微小RNA-145(miR-145)在乳腺癌中起着肿瘤抑制作用,但其在三阴性乳腺癌(TNBC)中的确切作用仍不清楚。在本研究中,通过茎环实时PCR分析了miR-145在人TNBC细胞和30例患者样本中的表达。我们发现miR-145在TNBC组织和细胞中显著下调。在HCC1937细胞中上调miR-145可显著抑制细胞增殖并诱导G1期阻滞,而MDA-MB-231细胞未显示出生长抑制。miR-145通过对TNBC细胞中新靶点基质金属蛋白酶11(MMP11)和Rab27a的转录后调控,在细胞侵袭中发挥抑制作用。此外,5-氮杂-2'-脱氧胞苷(DAC)可逆转miR-145的沉默。这些结果表明,miR-145通过靶向MMP11和Rab27a对TNBC恶性肿瘤具有抑制作用,这可能是TNBC潜在的治疗和诊断靶点。

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