Background: Kidney stones are composed of approximately 70–80% calcium oxalate. However, the exact mechanism of formation of calcium oxalate kidney stones remains unclear. In this study, we investigated the roles of endoplasmic reticulum stress (ERS), reactive oxygen species (ROS), and the NF-κB signalling pathway in the pathogenesis of oxalate-induced renal tubular epithelial cell injury and its possible molecular mechanisms. Methods: We established a model to evaluate the formation of kidney stones by intraperitoneal injection of glyoxylic acid solution into mice and assessed cell morphology, apoptosis, and the expression levels of ERS, ROS, and NF-κB signalling pathway-related proteins in mouse renal tissues. Next, we treated HK-2 cells with potassium oxalate to construct a renal tubular epithelial cell injury model. We detected the changes in autophagy, apoptosis, and mitochondrial membrane potential and investigated the ultrastructure of the cells by transmission electron microscopy. Western blotting revealed the expression levels of apoptosis and autophagy proteins; mitochondrial structural and functional proteins; and ERS, ROS, and NF-κB (p65) proteins. Lastly, we studied the downregulation of NF-κB activity in HK-2 cells by lentivirus interference and confirmed the interaction between the NF-κB signalling and ERS/ROS pathways. Results: We observed swelling of renal tissues, increased apoptosis of renal tubular epithelial cells, and activation of the ERS, ROS, and NF-κB signalling pathways in the oxalate group. We found that oxalate induced autophagy, apoptosis, and mitochondrial damage in HK-2 cells and activated the ERS/ROS/NF-κB pathways. Interestingly, when the NF-κB signalling pathway was inhibited, the ERS/ROS pathway was also inhibited. Conclusion: Oxalate induces HK-2 cell injury through the interaction between the NF-κB signalling and ERS/ROS pathways.

Predator species of animal can absorb plant microRNA that can regulate target gene expression and physiological function across species. The herb Lycium barbarum, a traditional Chinese medicine, has a wide range of antitumor effects. However, there are no reports on the effects of microRNA derived from it on the cross-border regulation of renal cell carcinoma (RCC). We performed in vitro and in vivo experiments to explore the role and mechanism of the L. barbarum-derived microRNA miR166a (Lb-miR166a) in cross-border regulation of RCC. Our mRNA sequencing analysis showed that Lb-miR166a regulates the expression of various genes in tumor cells, including 1232 upregulated genes and 581 downregulated genes, which were enriched to 1094 Gene Ontology entries and 43 Kyoto Encyclopedia of Genes and Genomes pathways. In vitro cell experiments confirmed that Lb-miR166a can inhibit the proliferation of RCC cells, promote the apoptosis of tumor cells, and inhibit the invasion and metastasis of tumor cells by regulating the expression of related genes. Furthermore, our in vivo tumor-bearing experiment showed that subcutaneous tumor formation volume decreased in Lb-miR166a mice, along with the number of liver metastases. This study elucidates the role and mechanism of Lb-miR166a in RCC treatment (Fig. 1). Our results further mechanistically confirm the antitumor properties of L. barbarum. Our study may contribute to the clinical development of a targeted drug for RCC treatment.

Background Renal cell carcinoma (RCC) is the seventh most common tumor worldwide. The incidence rate of RCC ranks second among urinary system tumors, and the incidence rate has been increasing in recent years. Recent studies have shown that plant miRNAs can be absorbed into organisms through diet, and can regulate target gene expression and physiological function of predators across species. As a traditional Chinese medicine, Lycium barbarum has a wide range of antitumor effects. However, there are no reports on the cross-border regulation of tumors by Lycium barbarum miRNA (Lb-miRNA). Methods Human RCC cells (Caki-1) were cultured in vitro. The overexpression group of Lb-miR166a was constructed using lentivirus transfection. The effect of Lb-miR166a on the expression of RCC cells was analyzed using transcriptome sequencing, and differentially expressed genes were screened. Combined with bioinformatics technology, the relevant mechanisms by which Lb-miR166a regulates the occurrence and development of RCC were screened and verified, and in vivo tumor-bearing experiments on nude mice verified the effect of Lb-miR166a expression on the occurrence, development, invasion, and metastasis of RCC. Results Transcriptome sequencing analysis showed that Lb-miR166a regulated the expression of a variety of genes in tumor cells and regulated a large number of signaling pathways related to tumor occurrence and development. The overall finding was that Lb-miR166a inhibited tumor cell proliferation, promoted tumor cell apoptosis, and inhibited cell invasion and metastasis. The tumor-bearing experiment in nude mice also showed that the subcutaneous tumor formation volume decreased in Lb-miR166a group mice, as did the expression of tumor cell Ki67 and the number of liver metastases. Conclusion This study explains the role of Lb-miR166a in the treatment of RCC and its underlying mechanisms. These results further improve the antitumor mechanism of L. barbarum and provide ideas for the clinical development of targeted drugs for the treatment of RCC.