MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression
Autor: | Xianrang Song, Li Xie, Jie Liu, Bao Song, Liyan Lv, Yan Zheng, Xingwu Wang, Ling Wei, Chuan-xi Wang |
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Jazyk: | angličtina |
Předmět: |
Cancer Research
Cellular differentiation Apoptosis Breast Neoplasms Biology medicine.disease_cause lcsh:RC254-282 Gene Expression Regulation Enzymologic Metastasis Breast cancer Cell Line Tumor microRNA medicine Humans Neoplasm Invasiveness Breast Neoplasm Metastasis RNA Processing Post-Transcriptional Cell Proliferation Tissue Inhibitor of Metalloproteinase-3 Matrigel Invasion Assay Research Cancer Cell Differentiation Tissue inhibitor of metalloproteinase medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gene Expression Regulation Neoplastic MicroRNAs Oncology Cancer research Female Carcinogenesis |
Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 29, Iss 1, p 29 (2010) Journal of Experimental & Clinical Cancer Research : CR |
ISSN: | 1756-9966 |
DOI: | 10.1186/1756-9966-29-29 |
Popis: | Background MicroRNAs are non-coding RNA molecules that posttranscriptionally regulate expression of target genes and have been implicated in the progress of cancer proliferation, differentiation and apoptosis. The aim of this study was to determine whether microRNA-21 (miR-21), a specific microRNA implicated in multiple aspects of carcinogenesis, impacts breast cancer invasion by regulating the tissue inhibitor of metalloproteinase 3 (TIMP3) gene. Methods miR-21 expression was investigated in 32 matched breast cancer and normal breast tissues, and in four human breast cancer cell lines, by Taqman quantitative real-time PCR. Cell invasive ability was determined by matrigel invasion assay in vitro, in cells transfected with miR-21 or anti-miR-21 oligonucleotides. In addition, the regulation of tissue inhibitor of metalloproteinase 3 (TIMP3) by miR-21 was evaluated by western blotting and luciferase assays. Results Of the 32 paired samples analyzed, 25 breast cancer tissues displayed overexpression of miR-21 in comparison with matched normal breast epithelium. Additionally, incidence of lymph node metastasis closely correlated with miR-21 expression, suggesting a role for miR-21 in metastasis. Similarly, each of the four breast cancer cell lines analyzed overexpressed miR-21, to varied levels. Further, cells transfected with miR-21 showed significantly increased matrigel invasion compared with control cells, whereas transfection with anti-miR-21 significantly decreased cell invasion. Evaluation of TIMP3 protein levels, a peptidase involved in extarcellular matrix degredation, inversely correlated with miR-21 expression. Conclusion As knockdown of miR-21 increased TIMP3 protein expression and luciferase reporter activity, our data suggests that miR-21 could promote invasion in breast cancer cells via its regulation of TIMP3. |
Databáze: | OpenAIRE |
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