LASP1 was initially identified in a cDNA library prepared from breast cancer metastases. The LASP1 protein includes three domains: an N-terminal LIM domain, a nebulin repeat domain and a C-terminal SH3 domain [27]. LASP1 is expressed at low basal levels in all normal human Selleckchem Capmatinib tissues, but is over-expressed in metastatic human breast cancer [28], ovarian cancer [29] and medulloblastoma [30]. Increased LASP1 expression could lead to a more aggressive breast carcinoma phenotype, and knocking down LASP1 may reduce the migratory capacity of breast cancer cells, possibly by influencing the localization of zyxin [29]. In our study, we identified the LASP1 transcript
as a target of miR-203 in TNBC cells and found that inhibition of TNBC cell migratory capacity was accompanied by a reduction in LASP1 expression. We also showed that repressing LASP1 expression by siRNA could significantly inhibit the migration of MDA-MB-231 cells, implying that LASP1 played a positive role in TNBC cell migration. GDC-0941 datasheet Moreover, we demonstrated
that decreased LASP1 expression is essential for the miR-203-mediated inhibition of TNBC cell migration, showing that the over-expression of LASP1 could partially rescue the migration inhibition induced by miR-203 in MDA-MB-231 cells. In conclusion, our data suggest that miR-203 could inhibit the proliferation and migration of TNBC cells by directly regulating the expression of BIRC5 and LASP1. Moreover, the activation of miR-203 may be a potentially useful novel strategy for inhibiting TNBC growth and metastasis. References 1. Jemal A, Bray F, I-BET-762 Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin 2011, 61:69–90.PubMedCrossRef 2. Pillai RS, Bhattacharyya SN, Artus CG, Zoller T, Cougot N, Basyuk E, Bertrand E, Filipowicz W: Inhibition
Glutamate dehydrogenase of translational initiation by Let-7 MicroRNA in human cells. Science 2005, 309:1573–1576.PubMedCrossRef 3. Pillai RS: MicroRNA function: multiple mechanisms for a tiny RNA? RNA 2005, 11:1753–1761.PubMedCrossRef 4. Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci 2004, 101:2999–3004.PubMedCrossRef 5. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR: MicroRNA expression profiles classify human cancers. Nature 2005, 435:834–838.PubMedCrossRef 6. Engels BM, Hutvagner G: Principles and effects of microRNA-mediated post-transcriptional gene regulation. Oncogene 2006, 25:6163–6169.PubMedCrossRef 7. Bartel DP, Chen CZ: Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 2004, 5:396–400.PubMedCrossRef 8.