Thus, this is the first to reveal that SGPP1 is a potent direct target of miR-27a, although the evidence of direction regulatory interaction is needed for further investigation. Limited studies have demonstrated that SGPP1 catalyzes the degradation of S1P via salvage and recycling of sphingosine into long-chain ceramides, and that aberrant expression of SGPP1 is associated with idiopathic pulmonary fibrosis, and pulmonary fibrosis. However, the biological functions for SGPP1 in carcinogenesis are largely unknown and worthy further elucidative. Smad2 is a member of the Smad family and is a key element in TGF-b signaling. Therefore, accompanying actions of TGF-b in different circumstances, e.g., in regulating development and differentiation in physiological cell process, and in facilitating cell growth and migration and angiogenesis in cancers, Smad2 exerts dual functions as tumor suppressor or oncogene. In the current study, we found that, similar as SGPP1, Samd2 expression at mRNA and protein levels was Molsidomine upregulated in colorectal cancers and cell lines, exhibiting oncogenic phenotypes; moreover, Smad2 was repressed at transcriptional and translational levels by miR-27a, suggesting the direct target of miR-27a, a novel finding that has not been reported previously. A few recent studies have reported that Smad2, similar as Smad3 and Smad4, is mutant in cancers, but Smad2 plays differential roles from Smad3 and Samd4 in TGF-b signaling. The Motolimod (VTX-2337) mutation frequency in colorectal cancer and whether the mutation of Smad2 leads to stability of SMAD2 protein in the colorectal cancer is not clear and warrants further investigation. Previous studies have also shown therapeutic role of Smad2, that blocking Smad2 could suppress TGF-b-induced tumorigenesis, epithelialmesenchymal transition, cell motility, and invasion, indicating that targeting miR-27a/Smad2 could have a great impact on developing a novel strategy for colorectal cancer therapy.The new signal pathway of miR-27a-Smad2-TGF-b could also contribute to the inhibitory role of miR-27a on cancer cell migration, invasion and metastasis, detailed mechanism is under investigation.