miRNA
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With the exception of nonmelanoma skin cancers, breast cancer is the most common cancer among women, with 1 in 8 women at risk for developing invasive breast cancer in their lifetime. In addition to invasive forms of breast cancer, the non-invasive, carcinoma in situ affects large numbers of women each year, with over 62,000 new cases expected in 2007. In addition to being one of the most common forms of cancer in women, breast cancer is the second leading cause of cancer death in women (second only to lung cancer). Men are not immune from the disease and can fall victim to either form of the disease, as well (though far less prevalent than occurrences in women). Genes related to breast cancer have been studied exhaustively, and several key players have been identified. Research has shown that women who have an abnormal BRCA1 or BRCA2 gene have up to an 85% risk of developing breast cancer by age 70 and are also at increased risk of developing ovarian cancer. Other genes involved in breast cancer include the tumor suppressor, p53, the recessive gene, ATM, and the previously identified p65 gene. In addition to the identification of key genes in breast cancer tumorigenesis, scientists have identified breast cancer-specific miRNAs that can act as either tumor suppressors or as oncogenes. Traditionally, miRNA expression has been tested using low-throughput techniques such as Northern-blot analysis and real-time PCR, but new developments in microarray technology now enable global profiling of all miRNA genes and their precursors in any sample type.
M-L Si and colleagues at Southern Illinois University School of Medicine (2006), profiled miRNA expression in matched normal breast tissue and breast tumor tissues by TaqMan real-time polymerase chain reaction miRNA array methods. Consistent with previous findings, the group found that miR-21 was highly overexpressed in breast tumors compared to the matched normal breast tissues. The group followed this analysis with transfection of breast cancer MCF-7 cells with anti-miR-21 oligonucleotides, finding that anti-miR-21 suppressed both cell growth in vitro and tumor growth in the xenograft mouse model associated with increased apoptosis and decreased cell proliferation. Together, these results suggested that miR-21 functions as an oncogene and modulates tumorigenesis through regulation of genes such as bcl-2 and thus, may serve as a novel therapeutic target.
Title: miR-21-mediated tumor growth.
Authors: Si ML, Zhu S, Wu H, Lu Z, Wu F,Mo YY
Journal: Oncogene. 2006 Oct 30; [Epub ahead of print]
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Anwar Hossain and researchers at the University of Texas (2006) examined Mir-17-5p regulation of breast cancer cell proliferation by inhibiting translation of AIB1 mRNA, finding that this miRNA had extensive complementarity to the mRNA of AIB1 (named for "amplified in breast cancer 1"). Cell culture experiments showed that AIB1 expression was downregulated by Mir-17-5p, primarily through translational inhibition and expression of Mir-17-5p was reduced in breast cancer cell lines. The group used traditional methods of Northern and Western blot analysis, coupled with assays for reporter genes, cell proliferation, and soft agar colony formation, to demonstrate an important role of Mir-17-5p in breast cancer cell proliferation and anchorage-independent growth by both overexpression and knockdown experiments. These results begin to shed light on revealed the role of Mir-17-5p as a tumor suppressor in breast cancer cells.
Title: Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA.
Authors: Hossain A, Kuo MT, Saunders GF
Journal: Mol Cell Biol, Vol 26, Issue 21: 8191-201
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An international collaborative effort between researchers in the United States and Italy (2005) examined microRNA gene expression deregulation in human breast cancer, using both Northern blot and microarray analysis to confirm the existence of a breast cancer–specific miRNA signature. Using these techniques, the group was able to identify the most significantly deregulated miRNAs (mir-125b, mir-145, mir-21, and mir-155), as well as miRNAs whose expression was correlated with specific breast cancer biopathologic features, such as estrogen and progesterone receptor expression, tumor stage, vascular invasion, or proliferation index. The findings of this study serve to increase understanding of the molecular basis of human breast cancer, suggesting that aberrant expression of miRNA genes may be important for the pathogenesis of breast cancer.
Title: MicroRNA gene expression deregulation in human breast cancer.
Authors: Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio , Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM
Journal: Cancer Res, Vol 65, Issue 16: 7065-70
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Title: Rapid alteration of microRNA levels by histone deacetylase inhibition.
Authors: Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC
Journal: Cancer Res, Vol 66, Issue 3: 1277-81
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Title: Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies.
Authors: Mattie MD, Benz CC, Bowers J,Sensinger K, Wong L, Scott GK, Fedele V, Ginzinger D, Getts R, Haqq C
Journal: Mol Cancer. 2006 Jun 19;5:24.
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Title: MicroRNA involvement in mammary gland development and breast cancer.
Authors: Silveri L, Tilly G, Vilotte JL, Le Provost F
Journal: Reprod Nutr Dev, Vol 46, Issue 5: 549-56
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Title: Frequent loss of Dab2 protein and infrequent promoter hypermethylation in breast cancer.
Authors: Bagadi SA, Prasad CP, Srivastava A, Prashad R, Gupta SD, Ralhan R
Journal: Breast Cancer Res Treat. 2006 Nov 18; [Epub ahead of print]
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