Self-assembled Cell Microarray for the Large-scale Identification of miRNA Regulating Cancer Cell Me

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  Metastasis is the overwhelming cause of mortality in patients with solid tumours.It is a complex and dynamic process,starting with local invasion,followed by intravasation into the systemic circulation,survival in the circulation,extravasation and establishment at distant tissues,and ultimately vascularization of the resulting tumours.Therefore,a more complete understanding of the molecular mechanism that regulates this process requires a detailed characterization of all metastasis-related traits.As a new class of signalling modulators,miRNAs have attracted great attention for certain unique features,including multi-target regulation,tissue specificity,and evolutionary conservation.By taking advantage of these advantages,this microarray has been extensively applied to the study of cancer metastasis,including cell autophagy,migration,invasion or angiogenesis [1-3].We found that over 20%miRNAs were unexpectedly found which have migratory regulation activity.Furthermore,the screening results revealed that the migratory miRNAs initially identified in a Hela cell-based screen are applicable to three other epithelial cancer cell lines as well as human primary endothelial cells.Since cell migration is a basic biological process,it is quite possible that a general involvement in migratory regulation is another distinctive feature of miRNAs.Therefore,it was believe that these findings advance the understanding of the physiological and therapeutic importance of miRNAs in cancer development,especially metastasis.Finally,miR-23b,which down-regulates in human colon cancer samples,potently mediates the multiple steps of metastasis,including tumour growth,invasion and evenangiogenesis in vivo.It regulates a cohort of prometastatic targets,including FZD7 or MAP3k1.These findings provide new insight into the physiologic and potentially therapeutic importance of miRNAs as a new class of functional modulators.
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