Regulation of microRNA Expression by Growth Factors in Tumor Development and Progression

MicroRNAs (miRNAs) are a class of noncoding small RNAs (22–25 nucleotides) that regulate cell proliferation and various cellular functions by interfering with the translation of target messenger RNAs (mRNAs). Altered expression of miRNAs is found in various human malignancies, and indeed, we previously reported that the expression of miR-205 and miR-21 was altered in human head and neck squamous cell carcinoma (HNSCC), by miRNA microarray analysis. We also confirmed that the expression of miR-200c and miR-27b was directly regulated by hepatocyte growth factor (HGF) in HNSCC cell line, HSC3. These results suggest the significance of miRNAs as a key regulatory molecule for achieving various functions of growth factors. Altered miRNA expression might contribute enhanced progressive and invasive characteristics, such as epithelial-mesenchymal transition (EMT), of malignant tumors by regulating the translation of growth factor-induced functional molecules. There are a growing number of reports that describe the translational regulation of growth factors, their receptors, and intracellular signaling molecules by miRNAs in various tumors. However, less of the reports describe the regulation of miRNA expression by a growth factor itself. In this article, we review the relation of tumor development and progression by growth factors with miRNA expression, especially the regulation of miRNA expression by growth factors, and focus on the cooperative interactions of miRNAs, their mRNA targets, and growth factor signaling, in the context of tumor progression.