RBMS3 at 3p24 inhibits nasopharyngeal carcinoma development via inhibiting cell proliferation, angiogenesis, and inducing apoptosis.

Deletion of the short arm of chromosome 3 is one of the most frequent genetic alterations in many solid tumors including nasopharyngeal carcinoma (NPC), suggesting the existence of one or more tumor suppressor genes (TSGs) within the frequently deleted region. A putative TSG RBMS3 (RNA binding motif, single stranded interacting protein 3), located at 3p24-p23, has been identified in our previous study. Here, we reported that downregulation of RBMS3 was detected in 3/3 NPC cell lines and 13/15 (86.7%) primary NPC tissues. Functional studies using both overexpression and suppression systems demonstrated that RBMS3 has a strong tumor suppressive role in NPC. The tumor suppressive mechanism of RBMS3 was associated with its role in cell cycle arrest at the G1/S checkpoint by upregulating p53 and p21, downregulating cyclin E and CDK2, and the subsequent inhibition of Rb-ser780. Further analysis demonstrated that RBMS3 had a pro-apoptotic role in a mitochondrial-dependent manner via activation of caspase-9 and PARP. Finally, RBMS3 inhibited microvessel formation, which may be mediated by down-regulation of MMP2 and β-catenin and inactivation of its downstream targets, including cyclin-D1, c-Myc, MMP7, and MMP9. Taken together, our findings define a function for RBMS3 as an important tumor suppressor gene in NPC.published_or_final_versio

Reply to profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

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Characterization of the role of EBV microRNAs in nasopharyngeal carcinoma

Meeting Abstract: 30

Reply to profiling of Epstein-Barr virus-encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

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Longitudinal study of viral loads and polyfunctional T cell responses towards epstein-barr virus in paediatric liver transplant recipients who developed post-transplant lymphoproliferative disorder

Poster PresentationOpen Access JournalThis journal issue (pp. 192-206) entitled: Proceedings of Congress: Joint Annual Scientific Meeting 2014: The Hong Kong Paediatric Society and Hong Kong Paediatric Nurses Association 15 June, 2014This study aims to investigate the long-term viral control and T-cell immunity towards Epstein-Barr virus (EBV) in paediatric liver transplant patients who developed posttransplant lymphoproliferative disorder (PTLD). We performed a longitudinal study on viral loads and T cell functions in six PTLD patients (two boys and four girls) up to 5 years after diagnosis. Median age at diagnosis was 2.4 years (range: 0.8-5.2 years). Primary disease was congenital biliary atresia with a median age of transplantation at 0.6 years (range: 0.5-1.3 years). Median time from date of transplantation to diagnosis of PTLD was 1.3 years (range: 0.3-4.7 years). All patients were seronegative towards EBV prior to transplantation and were maintained on a range of tacrolimus doses for immunosuppression. Three patients entered continual clinical remission after one course of rituximab while two patients had relapsed disease and one had persistent lymphocytosis requiring additional treatment with second course of rituximab or chemotherapy to enter clinical remission. Plasma EBV loads were determined by qPCR. Despite entering clinical remission, persistently elevated plasma loads were found in 4 of 6 patients indicating suboptimal long-term viral control. Two patients were selected for longitudinal profiling of EBV latent cycle and lytic cycle antigen-specific polyfunctional T-cell (PFC) responses from 1-4 years after PTLD diagnosis. Upon stimulation by overlapping peptides of EBNA1, EBNA3a/ 3b/3c and BZLF1, the production of three cytokines (IFN-, TNF-, IL-2) and expression of two cytotoxic markers (perforin, CD107a) were examined. Although CD4+ and CD8+ PFC responses could be detected at 3 years after diagnosis, the PFCs were predominantly perforinnegative and the proportion of PFCs with three-five functions was low ranging from 0-3 percent of total antigen-responsive T-cells. Long-term viral control is suboptimal concurrent with slow development of EBV-specific PFC responses signifying the continual risk of re-emergence of PTLD in this cohort of young PTLD patients

Longitudinal study of viral loads and polyfunctional T cell responses towards Epstein-Barr Virus in paediatric liver translplant recipients who developed post-transplant lymphoproliferative disorder

Conference Theme: Translating Discoveries into Prevention and Cure

Longitudinal study of viral loads and polyfunctional T cell responses towards Epstein-Barr virus in paediatric liver transplant recipients who developed post-transpleant lymphoproliferative disorder

Celebrating 50 years of Epstein-Barr Virus Discovery (1964-2014