METTL3-mediated upregulation of FAM135B promotes EMT of esophageal squamous cell carcinoma via regulating the Wnt/ß-catenin pathway.

Family with sequence similarity 135 member B (FAM135B) is a novel cancer-implicated gene in esophageal squamous cell carcinoma (ESCC). However, little is known regarding its biological functions and mechanisms in ESCC. Here, we identified FAM135B high expression was associated with lymph node metastasis and infiltrating development of ESCC. Elevated FAM135B expression promoted ESCC migration and invasion in vitro and lung metastasis in vivo. Furthermore, epithelial mesenchymal transition (EMT)-related pathways were enriched with differentially expressed genes (DEGs) in high FAM135B ESCC samples and FAM135B positively regulated EMT markers. Mechanistically, we observed FAM135B interacted with the intermediate domain of TRAF2 and NCK-interacting kinase (TNIK), activating the Wnt/ß-catenin signaling pathway. The facilitation of TNIK on ESCC migration and invasion was reversed by FAM135B siRNA. Additionally, N6-Methyladenosine (m6A) modification stabilized FAM135B mRNA and positively regulated FAM135B expression, with Methyltransferase like 3 (METTL3) as its substantial m6A writer. The pro-EMT effects of METTL3 overexpression were rescued by silencing FAM135B. Collectively, METTL3-mediated upexpression of FAM135B activated TNIK-dependent Wnt/ß-catenin pathway, highlighting the pivotal role of FAM135B driver in ESCC progression.

Adaptive extended state space predictive control for a kind of nonlinear systems.

This paper presents an adaptive nonlinear predictive control design strategy for a kind of nonlinear systems with output feedback coupling and results in the improvement of regulatory capacity for reference tracking, robustness and disturbance rejection. The nonlinear system is first transformed into an equal time-variant system by analyzing the nonlinear part. Then an extended state space predictive controller with a similar structure of a PI optimal regulator and with P-step setpoint feedforward control is designed. Because changes of the system state variables are considered in the objective function, the control performance is superior to conventional state space predictive control designs which only consider the predicted output errors. The proposed method is tested and compared with latest methods in literature. Tracking performance, robustness and disturbance rejection are improved.