Axin, a negative regulator of Wnt signaling, is a key scaffold protein for the b-catenin destruction complex. It has been previously shown that multiple post-translational modification enzymes regulate the level of Axin. Here, we provide evidence that protein arginine methyltransferase 1 (PRMT1) directly interacts with and methylates the 378th arginine residue of Axin both in vitro and in vivo. We found that the transient expression of PRMT1 led to an increased level of Axin and that knockdown of endogenous PRMT1 by short hairpin RNA reduced the level of Axin. These results suggest that methylation by PRMT1 enhanced the stability of Axin. Methylation of Axin by PRMT1 also seemingly enhanced the interaction between Axin and glycogen synthase kinase 3b, leading to decreased ubiquitination of Axin. Consistent with the role of PRMT1 in the regulation of Axin, knockdown of PRMT1 enhanced the level of cytoplasmic b-catenin as well as b-catenin-dependent transcription activity. In summary, we show that the methylation of Axin occurred in vivo and controlled the stability of Axin. Therefore, methylation of Axin by PRMT1 may serve as a finely tuned regulation mechanism for Wnt/b-catenin signaling.
The prevalence of asthma in Korea has increased over a recent 5-year period, and asthma is still suboptimally controlled. Public health strategies are needed to improve the management of asthma in adults.
The study aims to report the operative outcomes of robot-assisted thoracoscopic esophagectomy (RATE) with extensive mediastinal lymphadenectomy (ML) for intrathoracic esophageal cancer. We analyzed a prospective database of 114 consecutive patients who underwent RATE with lymph node dissection along recurrent laryngeal nerve (RLN) followed by cervical esophagogastrostomy. The study included 104 men with a mean age of 63.1 ± 0.8 years. Of these, 110 (96.5%) had squamous cell carcinoma, and the location of the tumor was upper esophagus in 7 (6.1%), middle in 62 (54.4%), and lower in 45 (39.5%). Preoperative concurrent chemoradiation was performed in 15 patients (13.2%). All but one patient underwent successful RATE, and R0 resection was achieved in 111 patients (97.4%). Extended ML and total ML were performed in 24 (21.1%) and 90 (78.9%) patients, respectively. Total operation time was 419.6 ± 7.9 minutes, and robot console time was 206.6 ± 5.2 minutes. The mean number of total, mediastinal, and RLN nodes was 43.5 ± 1.4, 24.5 ± 1.0, and 9.7 ± 0.7, respectively. The most common complication was RLN palsy (30, 26.3%), followed by anastomotic leakage (17, 14.9%) and pulmonary complications (11, 9.6%). Median hospital stay was 16 days, and 90-day mortality was observed in three patients (2.5%). On multivariate analysis, preoperative concurrent chemoradiation was a risk factor for pulmonary complications (odds ratio 7.42, 95% confidence interval 1.91-28.8, P = 0.004). RATE with extensive ML could be performed safely with acceptable postoperative outcomes. Long-term survival data should be followed in the future to verify the oncological outcome of the procedure.
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