SMAD2 and colorectal carcinoma: In this context, the most significantly affected functional pathways identified include, among others, TNF-alpha, SMAD2/3, TGF-beta, and Wnt signaling (Figure 4F), suggesting that specific PIWIL1–piRNA–mRNA interactions may be controlling essential cellular functions in CRC cells by post-transcriptional gene regulation mechanisms similar to those identified for PIWIL and piRNAs in germline cells.