miR-1286, a Tumor Suppressor of Gastric Cancer, Serves as a Promising Biomarker for Screening Gastric Cancer from Gastritis.

Gastric cancer (GC) is one of the crucial causes of cancer-associated death worldwide. This study aimed to investigate the biological function of miR-1286 in GC progression in vitro, evaluate the clinical value of serum miR-1286 to screen GC patients and explore its relationship with helicobacter pylori (HP) infection and peritoneal metastasis in GC patients. Expression of miR-1286 was measured by RT-qPCR. Cell Counting Kit-8 assay was utilized for measuring GC cell proliferation ability. The migration and invasion abilities of GC cells were measured using Transwell assays. Serum samples were obtained from 108 GC patients, 62 gastritis cases and 62 healthy volunteers. The diagnostic performance of miR-1286 was assessed using ROC analysis, and the predictive value of miR-1286 for peritoneal metastasis onset was analyzed using logistic regression analysis. miR-1286 played as a tumor suppressor in GC progression by inhibiting GC cell proliferation, migration and invasion. In GC patients, significantly decreased miR-1286 was observed compared to gastritis and healthy controls, and had considerable diagnostic accuracy to distinguish GC from the controls. A significant association was found between miR-1286 expression and HP infection, peritoneal metastasis and TNM stage. Moreover, miR-1286 was lowly expressed in GC patients with peritoneal metastasis, and independently predicted the occurrence of peritoneal metastasis in GC. miR-1286 acts as a tumor suppressor and a biomarker in GC, and is closely associated with HP infection and peritoneal metastasis onset. The methods to regulate miR-1286 may be novel strategies to improve the treatment of GC.

Long non-coding RNA LINC00649 regulates YES-associated protein 1 (YAP1)/Hippo pathway to accelerate gastric cancer (GC) progression via sequestering miR-16-5p.

Although long non-coding RNA (LncRNA) LINC00649 is reported to be closely associated with acute myeloid leukemia (AML), prostate cancer and colorectal cancer, its role in regulating other types of cancer, such as gastric cancer (GC), has not been studied. This study analyzed the expression status of LINC00649 in GC tissues and cells by performing Real-Time qPCR analysis, and we found that LINC00649 tended to be enriched in cancerous tissues and cells but not in their normal counterparts, which were supported by the data from TCGA dataset. Next, by performing the gain- and loss-of-function experiments, we expectedly found that LINC00649 acted as an oncogene to accelerate GC cell proliferation, migration and epithelial-mesenchymal transition (EMT) in vitro and promote its tumorigenesis in vivo. Moreover, the online miRDB software predicted that miR-16-5p bound to both LINC00649 and 3' untranslated region (3'UTR) of YAP1 mRNA, which were validated by the following dual-luciferase reporter gene system assay and RNA pull-down assay. Finally, we proved that LINC00649 exerted its tumor-promoting effects in GC by regulating the miR-16-5p/YES-associated protein 1 (YAP1)/Hippo pathway. Mechanistically, knock-down of LINC00649 suppressed YAP1 expressions by releasing miR-16-5p, resulting in the recovery of the Hippo pathway, which suppressed the expression levels of the downstream oncogenes, including EGFR, SOX2 and OCT4, leading to the inhibition of the malignant phenotypes in GC cells. In conclusion, this study, for the first time, evidenced that LINC00649 promoted GC progression by targeting the miR-16-5p/YAP1/Hippo signaling pathway, which provided potential diagnostic and therapeutic indicators for GC treatment for clinical utilization.

Encephalomyocarditis Virus Abrogates the Interferon Beta Signaling Pathway via Its Structural Protein VP2.

Type I interferon (IFN)-mediated antiviral responses are critical for modulating host-virus responses, and indeed, viruses have evolved strategies to antagonize this pathway. Encephalomyocarditis virus (EMCV) is an important zoonotic pathogen, which causes myocarditis, encephalitis, neurological disease, reproductive disorders, and diabetes in pigs. This study aims to understand how EMCV interacts with the IFN pathway. EMCV circumvents the type I IFN response by expressing proteins that antagonize cellular innate immunity. Here, we show that EMCV VP2 is a negative regulator of the IFN-ß pathway. This occurs via the degradation of the MDA5-mediated cytoplasmic double-stranded RNA (dsRNA) antiviral sensing RIG-I-like receptor (RLR) pathway. We show that structural protein VP2 of EMCV interacts with MDA5, MAVS, and TBK1 through its C terminus. In addition, we found that EMCV VP2 could significantly degrade RLRs by the proteasomal and lysosomal pathways. For the first time, EMCV VP2 was shown to play an important role in EMCV evasion of the type I IFN signaling pathway. This study expands our understanding that EMCV utilizes its capsid protein VP2 to evade the host antiviral response.IMPORTANCE Encephalomyocarditis virus is an important pathogen that can cause encephalitis, myocarditis, neurological diseases, and reproductive disorders. It also causes huge economic losses for the swine industry worldwide. Innate immunity plays an important role in defending the host from pathogen infection. Understanding pathogen microorganisms evading the host immune system is of great importance. Currently, whether EMCV evades cytosolic RNA sensing and signaling is still poorly understood. In the present study, we found that viral protein VP2 antagonized the RLR signaling pathway by degrading MDA5, MAVS, and TBK1 protein expression to facilitate viral replication in HEK293 cells. The findings in this study identify a new mechanism for EMCV evading the host's innate immune response, which provide new insights into the virus-host interaction and help develop new antiviral approaches against EMCV.