BackgroundCompared to the pulmonary lobe, the anatomical structure of the pulmonary segment is relatively complex and prone to variation, thus the risk and difficulty of segmentectomy is increased. We compared three‐dimensional computed tomography bronchography and angiography (3D‐CTBA) combined with 3D video‐assisted thoracic surgery (3D‐VATS) to perform segmentectomy to conventional two‐dimensional (2D)‐VATS for the treatment of non‐small cell lung cancer (NSCLC).MethodsWe retrospectively reviewed the data of randomly selected patients who underwent 3D‐CTBA combined with 3D‐VATS (3D‐CTBA‐VATS) or 2D‐VATS at the Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University Hospital, from January 2014 to May 2017.ResultsThe operative duration of 3D group was significantly shorter than the 2D group (P < 0.05). There was no significant difference in the number of dissected lymph nodes between the two groups (P > 0.05). The extent of intraoperative bleeding and postoperative drainage in the 3D group was significantly lower than in the 2D group (P < 0.05). Chest tube duration in the 3D group was shorter than in the 2D group (P < 0.05). Incidences of pulmonary infection, atelectasis, and arrhythmia were not statistically different between the two groups (P > 0.05). However, hemoptysis and pulmonary air leakage (>3d) occurred significantly less frequently in the 3D than in the 2D group (P < 0.05).Conclusion3D‐CTBA‐VATS is a more accurate and smooth technique and leads to reduced intraoperative and postoperative complications.

SMAD3 plays a central role in cancer metastasis, and its hyperactivation is linked to poor cancer outcomes. Thus, it is critical to understand the upstream signaling pathways that govern SMAD3 activation. Here, we report that SMAD3 undergoes methylation at K53 and K333 by EZH2, a process crucial for cell membrane recruitment, phosphorylation, and activation of SMAD3 upon TGFB1 stimulation.Mechanistically, EZH2-triggered SMAD3 methylation facilitates SMAD3 interaction with its cellular membrane localization molecule (SARA), which in turn sustains SMAD3 phosphorylation by the TGFB receptor. Pathologically, EZH2 expression increasing results in the accumulation of SMAD3 methylation to facilitate SMAD3 activation. EZH2-mediated SMAD3 K53/K333 methylation is upregulated and correlated with SMAD3 hyperactivation in breast cancer, promotes tumor metastasis, and is predictive of poor survival outcome. We used two TAT-peptides to abrogate SMAD3 methylation and therapeutically inhibit cancer metastasis. Collectively, these findings reveal the complicated layers in regulation of SMAD3 activation coordinated by EZH2-mediated SMAD3 K53/K333 methylation to drive cancer metastasis.

Perturbations in transforming growth factor-β (TGF-β) signaling can lead to a plethora of diseases, including cancer. Mutations and posttranslational modi cations (PTMs) of the partner of Smad complexes contribute to the dysregulation of TGF-β signaling. Here, we reported a PTM of Smad4, R361 methylation, that was critical for Smad complexes formation and TGF-β signaling activation. Through mass spectrometric, co-immunoprecipitation (Co-IP) and immuno uorescent (IF) assays, we found that oncogene protein arginine methyltransferase 5 (PRMT5) interacted with Smad4 under TGF-β1 treatment.Mechanically, PRMT5 triggered Smad4 methylation at R361 and induced Smad complexes formation and nuclear import. Furthermore, we emphasized that PRMT5 interacting and methylating Smad4 was required for TGF-β1-induced epithelial-mesenchymal transition (EMT) and colorectal cancer (CRC) metastasis, and Smad4 R361 mutation diminished PRMT5 and TGF-β1-induced metastasis. In addition, highly expressed PRMT5 or high level of Smad4 R361 methylation indicated worse outcomes in clinical specimens analysis. Collectively, our study highlights the critical interaction of PRMT5 and Smad4 and the roles of Smad4 R361 methylation for controlling TGF-β signaling during metastasis. We provided a new insight for Smad4 activation. And this study indicated that blocking PRMT5-Smad4 signaling might be an effective targeting strategy in Smad4 wide type CRC.