Expression and prognosis analysis of JMJD5 in human cancers.

Background: JumonjiC (JmjC) domain-containing protein 5 (JMJD5) plays an important part in cancer metabolism. However, the prognostic value of JMJD5 in most human cancers is unknown yet. We aimed to examine the expression level and prognostic value of JMJD5, immune cell infiltration in cancer patients, and simultaneously to examine the correlations among them. Materials and methods: The mRNA and protein expression of JMJD5 were analyzed through online Tumor Immune Estimation Resource (TIMER) or immunohistochemistry (IHC) of tissue microarray sections (TMAs) in cancer versus normal tissues. The Kaplan-Meier Plotter databases were used to assess the prognostic values. The connection between the expression of JMJD5 and the abundances of six infiltrating immune cells were explored by TIMER in breast cancer (BRCA), liver hepatocellular carcinoma (LIHC), lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD) and stomach adenocarcinoma (STAD). We used the Cox proportional hazards model to investigate the correlations among clinical outcome, the abundance of immune cell infiltration and JMJD5 expression. Results: We found that the JMJD5 expression was obviously lower in BRCA, LIHC and lung cancer (LUC) but higher in STAD than in normal tissues. High expression of JMJD5 had a better prognosis only in BRCA, LIHC and LUC but a worse prognosis in STAD. The expression of JMJD5 has a significant connection with the abundance of six kind of infiltrating immune cells. The expression of JMJD5 plus the number of immune-infiltrating B cells or macrophages may jointly serve as a prognostic marker in the above four cancers. Conclusion: We provided novel evidence of JMJD5 as an essential prognostic biomarker and perspective therapeutic target in BRCA, LUAD, LIHC and STAD.

PCAT-1 contributes to cisplatin resistance in gastric cancer through epigenetically silencing PTEN via recruiting EZH2.

The aim of this study was to investigate the functional role and the underlying molecular mechanism of long noncoding RNA (lncRNA) prostate cancer-associated transcript 1 (PCAT-1) in cisplatin resistance of gastric cancer (GC). Our results indicated that PCAT-1 was overexpressed in CDDP-resistant GC tumor tissues and cell lines. High expression of PCAT-1 was closely correlated with short overall survival in patients with GC. Downregulation of PCAT-1 resensitized CDDP-resistant GC cells to cisplatin. In addition, PCAT-1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. More importantly, PTEN silencing counteracted PCAT-1 knockdown-mediated enhancement in cisplatin sensitivity of CDDP-resistant GC cells. In summary, PCAT-1 led to cisplatin resistance in GC cells through epigenetically suppressing PTEN expression, providing a novel therapeutic strategy for GC patients with chemoresistance.