Lipopolysaccharide promotes NLRP3 inflammasome activation by inhibiting TFEB-mediated autophagy in NRK-52E cells.

The NLRP3 inflammasome is involved in many inflammatory diseases. Its activity must be strictly controlled to alleviate the inflammatory process. Autophagy plays a protective role in the negative regulation of NLRP3 inflammasome activation. However, the regulatory mechanism of autophagy controlling NLRP3 inflammasome activation remains to be further investigated. Here, we showed that in NRK-52E cells, lipopolysaccharide (LPS) and ATP stimulation significantly decreased mitochondrial membrane potential, increased ROS production and mtDNA copy number in cytosol. Moreover, autophagic flux was blocked when challenged with LPS and ATP as evidenced by increased LC3 II and p62 expression, reduced TFEB and CTSD expression, and impaired lysosomal acid environment. Furthermore, TFEB deficiency increased cytosolic mtDNA and enhanced LPS and ATP induced NLRP3 inflammasome activation and proinflammatory cytokine expression. Taken together, these findings reveal that LPS and ATP stimulation promoted NLRP3 inflammasome activation through inhibiting TFEB-mediated autophagy in NRK-52E cells, and TFEB could be a potential therapeutic target for the treatment of NLRP3 inflammasome-related kidney diseases.

miR-137 suppresses the invasion and procedure of EMT of human breast cancer cell line MCF-7 through targeting CtBP1.

Distant metastasis is the predominant site of gastric cancer recurrence and the most common cause of death. Recently, accumulating evidence has established that aberrant epithelial-mesenchymal transition activation plays a crucial role in the genesis, invasion, and metastasis of various cancers, including breast cancer. In this paper, we found that miR-137, which has been reported to function as a tumor suppressor in a variety of cancers, could significantly suppress the migration and invasion of MCF-7 cells, which might be correlated with its suppressive effects on the EMT procedure. Upon transfection, the epithelial marker, E-cadherin, was up-regulated, and the mesenchymal markers, N-cadherin and Vimentin, were suppressed. Moreover, we also found that carboxyl-terminal binding protein 1 (CtBP1) was a putative target gene of miR-137 in MCF-7 cells, and might be involved in the suppressive effects, which might provide novel diagnostic and therapeutic options for human breast cancer in the future.

miR-137 impairs the proliferative and migratory capacity of human non-small cell lung cancer cells by targeting paxillin.

Human lung cancer is the leading cause of cancer motility worldwide, with nearly 1.4 million deaths each year, among which non-small cell lung cancer (NSCLC) accounts for almost 85% of this disease. The discovery of microRNAs (miRNAs) provides a new avenue for NSCLC diagnostic and treatment regiments. Currently, a large number of miRNAs have been reported to be associated with the progression of NSCLC, among which serum miR-137 has been examined to be down-regulated in NSCLC patients. However, the function of miR-137 on NSCLC cells migration and invasion and the relative mechanisms were less known. Here, we found that ectopic expression of miR-137 could inhibit cell proliferation, induce cell apoptosis, and suppress cell migration and invasion in NSCLC cell line A549. Moreover, we found that paxillin (PXN) was a target gene of miR-137 in NSCLC cells and restored expression of PXN abolished the miR-137-mediated suppression of cell migration and invasion. Taken together, our results showed that miR-137 acted as a tumor suppressor in NSCLC by targeting PXN, and it may provide novel diagnostic and therapeutic options for human NSCLC clinical operation in future.