Esophageal squamous cell carcinoma (ESCC) is the major subtype of esophageal cancer with high aggressiveness and poor prognosis. There is an urgent need for understanding the molecular mechanism underlying the development and progression of ESCC. ESCC tissues and corresponding non-neoplastic tissues were collected. The expression and function of miR-124-3p and BCAT1 in two cell lines KYSE-150 and Eca109 were determined. We show downregulation of miR-124-3p expression in ESCC tissues, which is highly correlated with proliferation and migration of ESCC cell lines KYSE-150 and Eca109. miR-124-3p show high correlation with TNM stage and differentiation grade. Furthermore, miR-124-3p directly targets mRNA 3’UTR region of BCAT1, which results in upregulation of BCAT1 expression as observed in ESCC tissues and cell lines. Also, our data indicates that BCAT1 high expression is strongly linked to the disease-free survival, tumor size, pathologic stage, T classification and differentiation grade. On the other hand, we clarified the upstream mechanism regulating miR-124-3p expression in ESCC, which involves in the hypermethylation-silencing regulation mediated by DNA methyltransferase 1(DNMT1), which is of high expression in ESCC tissues and cell lines in the present study. In addition, DNMT1 knockdown or inhibition of DNMT1 function contributes to downregulation of miR-124-3p and BCAT1 expression. Our study thus clarifies a new mechanism that DNMT1/miR-124/BCAT1 axis regulates the development and progression of ESCC.

Background: The length of time for clinical improvement of patients with thymomatous myasthenia gravis (MG) after extended thymectomy is not clear. The purpose of this study was to determine the length of time after thymectomy in patients with thymomatous MG to achieve a 3-point reduction of Quantitative Myasthenia Gravis Score (QMGS), and identify variables associated with a failure to achieve the reduction. Methods: The records of patients with thymomatous MG who underwent extended thymectomy from January 2005 to December 2018 were retrospectively reviewed. The primary end point was a reduction of 3 points of QMGs and the secondary end point was another reduction of 3 points of QMGs. Results: A total of 481 patients were included in the analysis, the mean age of the patients was 41.63 ± 8.55 years, and approximately 60% were male. The median time to achieve a 3 point decrease in QMGS was 6 months, and the median time to achieve another 3 point decrease was 30 months. Multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a 3 point decrease in QMGS (HR = 0.55 and 0.65, respectively). Likewise, multivariable analysis indicated that age ≥ 42 years and Masaoka-Koga stage > I were associated with a lower probability of achieving a second 3 point decrease in QMGS (HR = 0.53 and 0.53, respectively). Conclusions: In patients with thymomatous MG who receive thymectomy, age ≥ 42 years and Masaoka-Koga stage > I are associated with a worse prognosis and failure to achieve a 3 point decrease in QMGS.