A Novel ceRNET Relying on the lncRNA JPX, miR-378a-3p, and Its mRNA Targets in Lung Cancer.

Lung cancer is the leading cause of cancer-related death worldwide. Non-coding RNAs are emerging as critical players for the onset and progression of cancer. Analyses of three different datasets revealed that the lncRNA JPX was overexpressed in adenocarcinoma tissues in comparison to normal lungs, as expected for an oncogene. Intriguingly, the predicted binding miR-378a-3p showed a significant inverse correlation with JPX expression. The lncRNA/miRNA physical interaction was validated by reporter vectors. Then, the oncogenic activity of JPX, the tumor-suppressive role of miR-378a-3p, and the contribution of their functional interaction to cancer hallmarks were demonstrated using assays for cell proliferation, migration, invasion, and 3D-spheroid formation. Finally, molecular circuits were investigated by boosting the expression of both JPX and miR-378a-3p, singularly and in combination, demonstrating that JPX counteracted miR-378a-3p silencing activity toward its oncogenic targets GLUT1, NRP1, YY1, and Wnt5a. Overall, the data unveil a novel ceRNET (competing endogenous RNA network), wherein JPX acts as a ceRNA by binding to miR-378a-3p, thus reducing the miRNA silencing activity toward its downstream targets, and eliciting oncogenic pathways driving lung cancer. The knowledge of the network may pave the way to develop new diagnostic panels, and innovative RNA-targeted and RNA-based therapeutic strategies.

Effect of Cannabidiolic Acid, N-Trans-Caffeoyltyramine and Cannabisin B from Hemp Seeds on microRNA Expression in Human Neural Cells.

Given the increasing interest in bioactive dietary components that can modulate gene expression enhancing human health, three metabolites isolated from hemp seeds-cannabidiolic acid, N-trans-caffeoyltyramine, and cannabisin B-were examined for their ability to change the expression levels of microRNAs in human neural cells. To this end, cultured SH-SY5Y cells were treated with the three compounds and their microRNA content was characterized by next-generation small RNA sequencing. As a result, 31 microRNAs underwent major expression changes, being at least doubled or halved by the treatments. A computational analysis of the biological pathways affected by these microRNAs then showed that some are implicated in neural functions, such as axon guidance, hippocampal signaling, and neurotrophin signaling. Of these, miR-708-5p, miR-181a-5p, miR-190a-5p, miR-199a-5p, and miR-143-3p are known to be involved in Alzheimer's disease and their expression changes are expected to ameliorate neural function. Overall, these results provide new insights into the mechanism of action of hemp seed metabolites and encourage further studies to gain a better understanding of their biological effects on the central nervous system.