The Wnt/β-catenin signaling pathway is a highly conserved pathway that is involved in cell development, proliferation, differentiation, apoptosis and autophagy. Among these processes, apoptosis and autophagy occur physiologically during host defense and the maintenance of intracellular homeostasis. Mounting evidence suggests that the crosstalk between Wnt/β-catenin-regulated apoptosis and autophagy has broad functional significance in various diseases. Herein, we summarize the recent studies in understanding the role of the Wnt/β-catenin signaling pathway in apoptosis and autophagy, and draw the following conclusions: a) For apoptosis, the regulation of Wnt/β-catenin is generally positive. However, a small amount of evidence indicates the presence of a negatively regulated relationship between Wnt/β-catenin and apoptosis; b) Wnt/β-catenin influences the occurrence and development of autophagy by regulating autophagy-related factors, and these factors in turn affect Wnt/β-catenin pathway; c) Wnt/β-catenin always balances the molecular damage caused by the crosstalk between autophagy and apoptosis in a compensatory manner. Understanding the specific role of the Wnt/β-catenin signaling pathway during different stages of autophagy and apoptosis may provide new insights into the progression of related diseases regulated by the Wnt/β-catenin signaling pathway.

Emerging evidence suggests that long non-coding RNAs (LncRNAs) are involved in Mtb-induced programmed necrosis. Among these LncRNAs, LncRNA NR_003508 is associated with LPS-induced acute respiratory distress syndrome. However, whether LncRNA NR_003508 contributes to Mtb-induced programmed necrosis remains undocumented. Firstly, the expression of LncRNA NR_003508 was determined using RT-qPCR and FISH. The protein expression of RIPK1, p-RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL was measured by Western blot in RAW264.7 and mouse lung tissues. Furthermore, luciferase reporter assays and bioinformatics were used to predict specific miRNA (miR-346-3p) and mRNA (RIPK1) regulated by LncRNA NR_003508. In addition, RT-qPCR was used to detect the RIPK1 expression in TB patients and healthy peripheral blood. The flow cytometry assay was performed to detect cell necrosis rates. Here we show that BCG infection-induced cell necrosis and increased LncRNA NR_003508 expression. si-NR_003508 inhibited BCG/H37Rv-induced programmed necrosis in vitro or in vivo. Functionally, LncRNA NR_003508 has been verified as a ceRNA for absorbing miR-346-3p, which targets RIPK1. Moreover, RIPK1 expression was elevated in the peripheral blood of TB patients compared with healthy people. Knockdown of LncRNA NR_003508 or miR-346-3p overexpression suppresses cell necrosis rate and ROS accumulation in RAW264.7 cells. In conclusion, LncRNA NR_003508 functions as a positive regulator of Mtb-induced programmed necrosis via sponging miR-346-3p to regulate RIPK1. Our findings may provide a promising therapeutic target for tuberculosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by epithelial-mesenchymal transition (EMT) as a key pathological feature. The molecular mechanism of EMT is not fully understood. Hence, the current study aimed to investigate the pathogenesis of EMT, which focus on the function of Epithelial Splicing Regulatory Protein 1 (ESRP1) in regulating EMT. Methods: The present study utilized bleomycin (BLM) to establish mouse models of IPF. Then, single-cell RNA sequencing (scRNA-seq) of entire lung tissue was employed to delineate transcriptional alterations in epithelial cells and to nominate prospective regulators of EMT. The target gene was subsequently validated in vivo and in vitro by qPCR, western blot, and immunofluorescence. Furthermore, an EMT model was established in TGF-β1–treated MLE-12 alveolar epithelial cells. Lentivirus or siRNA was hired to modulate the expression of target gene and elucidate its mechanistic contribution to EMT. Results: ScRNA-seq revealed marked up-regulation of the ESRP1 in alveolar epithelial cells compared with PBS-treated controls. Subsequent mechanistic interrogation in primary and MLE-12 alveolar epithelial cells demonstrated that knockdown of ESRP1 suppressed, whereas its overexpression potentiated, the expression of Epac, Rap1a, and N-cad which were key effectors of EMT. Importantly, Co-IP (Co-Immunoprecipitation) showed that there was interaction between ESRP1, Epac, and Rap1a. Silencing of either Epac or Rap1a did not reciprocally alter ESRP1 expression, confirming an upstream regulatory hierarchy. Conclusion: Our findings demonstrate that ESRP1 upregulation in alveolar epithelial cells drives IPF progression by promoting EMT via the Epac–Rap1a axis.