DIAPH3, a member of the formin proteins, has the capacity to nucleate and elongate actin filaments, thus remodeling the cytoskeleton [2]. It is involved in pathways such as the ERK signaling pathway [1,3]. DIAPH3 is essential for cytokinesis, and its dysfunction can lead to multinucleated cells. It also plays a role in mitosis by regulating the assembly and bipolarity of the mitotic spindle [2].

In hepatocellular carcinoma (HCC), LINC01089, a super enhancer-driven lncRNA, can induce alternative splicing of DIAPH3 by interacting with hnRNPM, leading to skipping of exon 3. Loss of LINC01089 increases DIAPH3 protein levels, suppressing the ERK/Elk1/Snail axis and inhibiting EMT of HCC cells [1]. In lung adenocarcinoma, DIAPH3 is up-regulated and promotes cell growth by interacting with STK38, impairing the interaction between STK38 and MEKK, and activating ERK signaling [3]. In pancreatic cancer, DIAPH3 is highly expressed and promotes cancer progression by activating selenoprotein TrxR1-mediated antioxidant effects [4]. In colorectal cancer, DIAPH3 is down-regulated, and its knockdown promotes cell proliferation and migration by inhibiting EGFR transportation to lysosome [5]. Conditional inactivation of Diaph3 in mouse cerebral cortex disrupts neurogenesis, leading to cortical malformation and autistic-like behavior [2].

In conclusion, DIAPH3 is crucial for cytoskeleton remodeling, cytokinesis, and mitosis. Its dysregulation is associated with various cancers including HCC, lung, pancreatic, and colorectal cancers, as well as neurodevelopmental disorders. Studies using conditional knockout mouse models have revealed its role in these disease conditions, providing insights into the underlying molecular mechanisms and potential therapeutic targets.