Search

Objective: To investigate the relationship between hematologic tumors and Epstein-Barr virus (EBV)-encoded small noncoding RNA (EBER) variations as well as latent membrane protein 1 (LMP1) variations. Methods: Patients with leukemia and myelodysplastic syndrome (MDS) were selected as subjects. Genotypes 1/2 and genotypes F/f were analyzed using the nested PCR technology, while EBER and LMP1 subtypes were analyzed by the nested PCR and DNA sequencing. Results: Type 1 was more dominant than type 2, found in 59 out of 82 (72%) leukemia and in 31 out of 35 (88.6%) MDS, while type F was more prevalent than type f in leukemia (83/85, 97.6%) and MDS (29/31, 93.5%) samples. The distribution of EBV genotypes 1/2 was not significantly different among leukemia, MDS, and healthy donor groups, neither was that of EBV genotypes F/f. EB-6m prototype was the dominant subtype of EBER in leukemia and MDS (73.2% [30/41] and 83.3% [10/12], respectively). The frequency of EB-6m was lower than that of healthy people (96.7%, 89/92), and the difference was significant (p < 0.05). China 1 subtype was the dominant subtype of LMP1 in leukemia and MDS (70% [28/40] and 90% [9/10], respectively), and there was no significant difference in the distribution of LMP1 subtypes among the 3 groups (p > 0.05). Conclusion: The distribution of EBV 1/2, F/f, EBER, and LMP1 subtypes in leukemia and MDS was similar to that in the background population in Northern China, which means that these subtypes may be rather region-restricted but not associated with leukemia and MDS pathogenesis. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is a unique type of gastric carcinomas that promoter hypermethylation of tumor-related genes is extremely frequent to be found. Aquaporin 3 (AQP3) is a small membrane transport protein that plays a crucial role in cancer progression and metastasis. However, there is no experimental study on the expression of AQP3 in EBVaGC and the regulation mechanism of EBV on AQP3. In this study, the loss of AQP3 was contributed by the hypermethylation status of AQP3 promoter in EBVaGC which was caused by elevated expression of DNMT3a. In addition, stable and transient transfection system in SGC7901 showed that viral latent membrane protein 2A (LMP2A) activated phosphorylated ERK and up-regulated DNMT3a. Taken together, LMP2A induced the phosphorylation of ERK, which activated DNMT3a transcription and caused AQP3 expression loss through CpG island methylation of AQP3 promoter in EBVaGC. [ABSTRACT FROM AUTHOR]

Highlights • The relative expression of miR-BART16 is higher in EBVaGC tissues than cell lines. • Overexpression of miR-BART16 could reduce the LMP1 mRNA and protein levels. • Inhibition the endogenous miR-BART16 increases the LMP1 mRNA and protein level. • BART16 has a vital role on cell proliferation in EBV-associated gastric carcinoma. Abstract Epstein–Barr virus (EBV) is a ubiquitous oncogenic herpesvirus associated with various human tumors. Latent membrane protein (LMP) 1 is considered a key oncoprotein in some EBV-associated tumors, while it is absent in EBV-associated gastric carcinoma (EBVaGC). In the present study, we did not detect the mRNA or the protein expression of LMP1 in 10 EBVaGC tissue samples, but we found that miRNA-BART16 was more abundantly expressed in EBVaGC primary tissues than in cell lines. It has been reported that EBV-encoded miRNA-BART16 can target the 3′-untranslated regions of LMP1 and negatively regulate its expression. When a BART16 inhibitor or mimics were transfected into EBVaGC cell lines, both mRNA and protein levels were changed compared with those in controls. We further investigated the role of miRNA-BART16 in EBVaGC. According to the CCK8 assay, the proliferation of GT38 and GT39 cells increased after treatment with a miRNA-BART16 inhibitor. At the same time, the BART16 inhibitor caused increased accumulation of G2/M phase cells by bromodeoxyuridine and propidium iodide staining analysis. In addition, no obvious difference was observed in apoptosis after treatment with an inhibitor or mimics using annexin V staining. Our findings highlight the viral role of EBV-encoded miRNA-BART16 in regulating oncogenic LMP1 expression and a negative association with the proliferation of EBVaGC. [ABSTRACT FROM AUTHOR]

• LMP1 and LMP2A inhibit the expression of COX-2 in EBVaGC. • TRAF2 is involved in the inhibitory effect of LMP1/2A on COX-2. • LMP1 also down-regulates COX-2 by reducing phosphorylation of ERK. Epstein-Barr virus-associated gastric cancer (EBVaGC) accounts for nearly 10% of gastric cancer. Cyclooxygenase-2 (COX-2) plays a crucial role in cancer progression. However, there is no experimental study on the regulation mechanism of EBV on COX-2 in EBVaGC. To understand more about the tumorigenic mechanism of EBVaGC, the study investigated the role of EBV encode latent membrane protein LMP1 and LMP2A in the regulation of COX-2. The expression of COX-2 was examined in EBVaGC and EBV negative gastric cancer (EBVnGC) cell lines. The plasmids were transfected in SGC7901 to overexpress LMP1/2A. Small interfering RNA (si-RNA) targeting LMP1/2A in GT38 and targeting TRAF2 in SGC7901 were used to detect the expression of COX-2. Furthermore, si-ERK1/2 and the MEK inhibitor PD0325901 were used to investigate whether p-ERK participate in the regulation of COX-2 in SGC7901. The overexpression of LMP1 or LMP2A in SGC7901 down-regulates both COX-2 and TRAF2 expression, and knockdown of LMP1 or LMP2A in GT38 resulted in a certain recovery of COX-2 and TRAF2 expression. Moreover, si-TRAF2 indicated that a sharp down-regulation of COX-2. And the decrease of p-ERK also mediates the inhibitory effect of LMP1 on COX-2. In summary, overexpression of LMP1 and LMP2A inhibits COX-2, which is mediated by a decrease of TRAF2, and p-ERK is involved in the inhibition of COX-2 by LMP1 in gastric cancer. [ABSTRACT FROM AUTHOR]