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Peritoneal metastasis is the most frequent cause of death in patients with advanced gastric carcinoma (GC). The phosphatase of regenerating liver-3 (PRL-3) is recognized as an oncogene and plays an important role in GC peritoneal metastasis. However, the mechanism of how PRL-3 regulates GC invasion and metastasis is unknown. In the present study, we found that PRL-3 presented with high expression in GC with peritoneal metastasis, but phosphatase and tensin homologue (PTEN) was weakly expressed. The p-PTEN/PTEN ratio was also higher in GC with peritoneal metastasis than that in the normal gastric tissues. We also found the same phenomenon when comparing the gastric mucosa cell line with the GC cell lines. After constructing a wild-type and a mutant-type plasmid without enzyme activity and transfecting them into GC SGC7901 cells, we showed that only PRL-3 had enzyme activity to downregulate PTEN and cause PTEN phosphorylation. The results also showed that PRL-3 increased the expression levels of MMP-2/MMP-9 and promoted the migration and invasion of the SGC7901 cells. Knockdown of PRL-3 decreased the expression levels of MMP-2/MMP-9 significantly, which further inhibited the migration and invasion of the GC cells. PRL-3 also increased the expression ratio of p-Akt/Akt, which indicated that PRL-3 may mediate the PI3K/Akt pathway to promote GC metastasis. When we transfected the PTEN siRNA plasmid into the PRL-3 stable low expression GC cells, the expression of p-Akt, MMP-2 and MMP-9 was reversed. In conclusion, our results provide a bridge between PRL-3 and PTEN; PRL-3 decreased the expression of PTEN as well as increased the level of PTEN phosphorylation and inactivated it, consequently activating the PI3K/Akt signaling pathway, and upregulating MMP-2/MMP-9 expression to promote GC cell peritoneal metastasis.

Colon cancer (CC) is one of the most frequent malignancies in the world, with a high rate of morbidity and death. In CC, necroptosis and long noncoding RNA (lncRNAs) are crucial, but the mechanism is not completely clear. The goal of this study was to create a new signature that might predict patient survival and tumor immunity in patients with CC. Expression profiles of necroptosis-related lncRNAs in 473 patients with CC were retrieved from the TCGA database. A consensus clustering analysis based on differentially expressed (DE) genes and a prognostic model based on least absolute shrinkage and selection operator (LASSO) regression analysis were conducted. Clinicopathological correlation analysis, expression difference analysis, PCA, TMB, GO analysis, KEGG enrichment analysis, survival analysis, immune correlation analysis, prediction of clinical therapeutic compounds, and qRT–PCR were also conducted. Fifty-six necroptosis-related lncRNAs were found to be linked to the prognosis, and consensus clustering analysis was performed. There were substantial variations in survival, immune checkpoint expression, clinicopathological correlations, and tumor immunity among the different subgroups. Six lncRNAs were discovered, and patients were split into high-risk and low-risk groups based on a risk score generated using these six lncRNAs. The survival time of low-risk patients was considerably longer than that of high-risk patients, indicating that these lncRNAs are directly associated with survival. The risk score was associated with the tumor stage, infiltration depth, lymph node metastasis, and distant metastasis. After univariate and multivariate Cox regression analysis, the risk score and tumor stage remained significant. Cancer- and metabolism-related pathways were enriched by KEGG analyses. Immune infiltration was shown to differ significantly between high- and low-risk patients in a tumor immunoassay. Eight compounds were screened out, and qRT–PCR confirmed the differential expression of the six lncRNAs. Overall, in CC, necroptosis-related lncRNAs have an important function, and the prognosis of patients with CC can be predicted by these six necroptosis-related lncRNAs. They may be useful in the future for customized cancer therapy.