Recent studies have shown that competing endogenous RNAs (ceRNAs) play an important role in the regulation of gene expression, and participate in a wide range of biological processes, including carcinogenesis. Long non-coding RNA PTENP1, the pseudogene of PTEN tumor suppressor, has been reported to exert its tumor suppressive function via modulation of PTEN expression in many malignancies. However, whether a PTENP1∼miRNA∼PTEN ceRNA network exists and how it functions in gastric cancer (GC) remains elusive. In order to identify and characterize the PTENP1∼miRNA∼PTEN ceRNA network in GC, we first determined PTENP1 levels in clinical GC samples and found that PTENP1 and PTEN were concurrently downregulated in these samples. We further demonstrated that PTENP1 could act as a ceRNA to sponge miR-106b and miR-93 from targeting PTEN for downregulation using a novel ceRNA in vitro gradient assay. Thus, we revealed a tumor suppressive role of PTENP1 as ceRNA in GC and pinpointed the specific miRNAs decoyed by PTENP1, highlighting the emerging roles of ceRNAs in the biological regulation of GC cells and their possible clinical significance.

Purpose: To investigate the potential mechanism underlying the anti-gastric cancer (GC) effect of Oldenlandia diffusa using network pharmacology, and to provide scientific guidance for subsequent pharmacological and clinical translational studies. Methods: The potential bioactive compounds in Oldenlandia diffusa and their related targets were obtained through TCMSP online platform. The GeneCards and MalaCards databases were used to search for GC-related disease targets. The targets shared by the two databases were entered into STRING protein interactions online database to obtain the interaction network of potential therapeutic targets. These were further screened for potential core targets through MCODE plugin. Cytoscape 3.2.1 software was used to construct the "component-target-disease" and PPI network, while GO and KEGG enrichment analyses were performed using DAVID v6.8 online software. Results: Seven bioactive components and 180 drug targets were screened in Oldenlandia diffusa, out of which 167 targets were co-activated with GC, and 28 potential core targets were identified. The results of GO function enrichment analysis of the hub targets showed that they were related to gene transcription and expression, cytokine-mediated signaling pathway and inflammation response. The results of KEGG signaling pathway enrichment analysis showed that they were mainly associated with cancer signaling, IL-17-related signaling and TNF signaling pathways. Conclusion: Oldenlandia diffusa exerts its therapeutic effect on GC through multi-component, multi-target and multi-signaling pathways. This finding provides novel evidence for the application of Oldenlandia diffusa in GC treatment.