SMAD4 and cancer: For example, the miR-17-92 cluster (11), including miR-17 and miR-20a, has been implicated in modulating the TGF-β signaling pathway by targeting SMAD2, SMAD4, and TGFBR2, contributing to cancer progression, and miR-26a (12) has been identified as a tumor suppressor in multiple cancers, including hepatocellular carcinoma, by directly targeting Cyclin D2 and Cyclin E2, leading to G1 phase cell cycle arrest.