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The NOTCH2 gene plays a role in the development of many tumors. Deltex E3 ubiquitin ligase 3 (DTX3) was identified as a novel E3 ligase for NOTCH2 and as a potential therapeutic target for esophageal cancer. However, whether DTX3 could regulate NOTCH2 to suppress the progression of esophageal carcinoma remains unknown. In our study, NOTCH2 had higher expression in human esophageal carcinoma cell lines compared to normal human esophageal epithelial cell line, and ablation of NOTCH2 suppressed the proliferation and migration of esophageal carcinoma cells. A novel E3 ligase for NOTCH2 was identified by yeast two‐hybrid (Y2H) screening, and DTX3 promoted the ubiquitination and degradation of NOTCH2. Further study showed that DTX3 overexpression suppressed the proliferation and tumorigenicity of human oesophageal carcinoma cells. The analysis of tissue samples from patients revealed that the expression of NOTCH2 was high while the expression of DTX3 was low in esophageal cancer. Furthermore, the expression of DTX3 and NOTCH2 showed a significant negative correlation in human oesophageal cancer samples. Our study suggested that the DTX3‐NOTCH2 axis plays an important role in the progression of esophageal cancer, and DTX3 acts as an anti–oncogene in esophageal carcinoma, potentially offering a therapeutic target for esophageal cancer.

Central precocious puberty (CPP), largely caused by germline mutations in the MKRN3 gene, has been epidemiologically linked to cancers. MKRN3 is frequently mutated in non–small cell lung cancers (NSCLCs) with five cohorts. Genomic MKRN3 aberrations are significantly enriched in NSCLC samples harboring oncogenic KRAS mutations. Low MKRN3 expression levels correlate with poor patient survival. Reconstitution of MKRN3 in MKRN3-inactivated NSCLC cells directly abrogates in vitro and in vivo tumor growth and proliferation. MKRN3 knockout mice are susceptible to urethane-induced lung cancer, and lung cell–specific knockout of endogenous MKRN3 accelerates NSCLC tumorigenesis in vivo. A mass spectrometry–based proteomics screen identified PABPC1 as a major substrate for MKRN3. The tumor suppressor function of MKRN3 is dependent on its E3 ligase activity, and MKRN3 missense mutations identified in patients substantially compromise MKRN3-mediated PABPC1 ubiquitination. Furthermore, MKRN3 modulates cell proliferation through PABPC1 nonproteolytic ubiquitination and subsequently, PABPC1-mediated global protein synthesis. Our integrated approaches demonstrate that the CPP-associated gene MKRN3 is a tumor suppressor.

Background: To evaluate the safety and efficacy of single incision plus one (SI+1) port three-dimensional (3D) laparoscopic minimally invasive esophagectomy (MIE). Methods: Clinical data of patients who underwent 3D thoracic laparoscopic MIE in our department from September 2020 to March 2021 were analyzed retrospectively. According to the different methods of laparoscopic surgery, the patients were divided into 2 groups: SI+1 port 3D laparoscopy group and multiportal 3D laparoscopy group. The operation time of the 3D laparoscopy component, amount of intraoperative blood loss, number of celiac lymph node dissections, postoperative abdominal drainage days, postoperative total abdominal drainage, postoperative complications, and length of hospital stay were analyzed. Results: There was no significant difference between the 2 methods in laparoscopic operation time (30.11±5.86 vs. 28.45±4.72 min, P=0.49), intraoperative blood loss (34.44±9.82 vs. 35.91±6.25 mL, P=0.69), number of celiac lymph node dissections (8.44±3.13 vs. 7.09±2.12, P=0.27), postoperative abdominal drainage days (3.11±0.33 vs. 3.00±0.00 days, P=0.28), postoperative total abdominal drainage (95.00±23.33 vs. 92.27±11.26 mL, P=0.74), postoperative complications (22.2% vs. 27.3%, P=0.33), and hospital stay (9.67±0.71 vs. 10.18±0.87 days, P=0.17). None of the patients enrolled in the study had recurrence or death to date. Conclusions:The application of SI+1 port 3D laparoscopy in minimally invasive resection of esophageal carcinoma is safe and feasible.