Inhibition of transforming growth factor beta/SMAD signal by MiR-155 is involved in arsenic trioxide-induced anti-angiogenesis in prostate cancer.
Bottom Line: Furthermore, As2 O3 improved the expression of miR-155 via DNA-demethylation.MiR-155, which targeted the SMAD2-3'UTR, decreased the expression and function of SMAD2.Knockdown of miR-155 abolished the As2 O3 -induced inhibitions of the TGF-β/SMAD2 signaling, the vascular endothelial growth factor secretion and angiogenesis.
Affiliation: Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.Show MeSH
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Mentions: Finally, we investigated the effects of As2O3 on the miR-155/SMAD2 signal pathway and on angiogenesis in vivo. As shown in Figure 6(a), As2O3 decreased the tumor growth. However, the body weight and liver weight were similar in both vehicle and CaA-treated mice (Table S3). In addition, in the As2O3-treated group, there was increased expression of miR-155 but decreased expressions of VEGF and SMAD2 mRNA (Fig. 6b–d). Importantly, As2O3 exposure decreased the expressions of CD31 (a vessel density marker(22)) mRNA and protein (Fig. 6e,f). The MVD was also decreased by As2O3 (Fig. 6g). These results indicate that As2O3 improved the miR-155 but inhibited the SMAD2 and angiogenesis in vivo.
Affiliation: Affiliated Nanjing Maternity and Child Health Care Hospital, Nanjing Medical University, Nanjing, China.