AR can then suppress this R-2HG/circRNA-51217/miRNA-646/TGFβ1/p-Smad2/3 signaling-increased PCa cell invasion via repressing TGFβ1 transcription and inhibiting circRNA-51217 expression through regulating ADAR2 expression.
Increased activin-β<sub>A</sub> and -β<sub>C</sub> subunit immunoreactive scores and decreased Smad-2 nuclear localization were also evident in human prostate cancer.
Subsequently, we confirmed that thymoquinone repressed metastasis and EMT of prostate cancer through downregulation of the TGF-β/Smad2/3 signaling pathway, which may be partially reversed by TGF-β overexpression.
Although Smad2 resides within LCR 1, it was not mutated in any of the six prostate cell lines (five prostate cancer cell lines and one immortalized prostate epithelial cell line) analysed, suggesting that it is not a candidate TSG in prostate cancer.