Primary cilia are critically involved in the coordination of diverse signaling pathways and ciliary defects are associated with a variety of human diseases. The past decades have witnessed great progress in the core machinery orchestrating ciliary assembly. However, the upstream epigenetic cues that direct ciliogenesis remain elusive. Herein, we demonstrate that mixed-lineage leukemia protein 2 (MLL2), a histone methyltransferase, plays a negative role in ciliogenesis. RNA-sequencing analysis reveals that the expression of five actin-associated proteins is significantly downregulated in MLL2-depleted cells. Overexpression of these proteins partially rescues ciliary abnormality elicited by MLL2 depletion. Our data also show that actin dynamics is remarkably changed in MLL2-depleted cells, resulting in the impairment of cell adhesion, spreading, and motility. In addition, MLL2 depletion promotes ciliary vesicle trafficking to the basal body in an actin-related manner. Together, these results reveal that MLL2 inhibits ciliogenesis by modulating actin dynamics and vesicle transport, and suggest that alteration of MLL2 may contribute to the pathogenesis of cilium-associated diseases.

Successful treatment of pancreatic cancer, which has the highest mortality rate among all types of malignancies, has challenged oncologists for decades, and early detection would undoubtedly increase favorable patient outcomes. The identification of proteins involved in pancreatic cancer progression could lead to biomarkers for early detection of this disease. This study identifies one potential candidate, cylindromatosis (CYLD), a deubiquitinase and microtubule‐binding protein that plays a suppressive role in pancreatic cancer development. In pancreatic cancer samples, downregulation of CYLD expression resulted from a loss in the copy number of the CYLD gene; additionally, reduced expression of CYLD negatively correlated with the clinicopathological parameters. Further study demonstrated that CYLD deficiency promoted colony formation in vitro and pancreatic cancer growth in vivo. Mechanistic studies revealed that CYLD is essential for spindle orientation and properly oriented cell division; CYLD deficiency resulted in a substantial increase in chromosome missegregation. Taken together, these data indicate a critical role for CYLD in suppressing pancreatic tumorigenesis, implicating its potential as a biomarker for early detection of pancreatic cancer and a prognostic indicator of patient outcomes.