SMAD2 and neoplasm: Our functional analysis also revealed that the deregulated piRNAs may affect the TGF-beta pathway, specifically by targeting the genes BMP5, BMPR1A, SMAD2, and TGFB3. This pathway plays key roles in carcinogenesis and its deregulation is involved in a cascade of aberrant events that trigger cell growth and proliferation pathways, such as JNK and ERK, contributing to tumor progression, cell invasion, and metastasis [66].