Nasopharyngeal carcinoma (NPC) is a highly metastatic tumor characterized by close association with EBV. Of the EBV-encoded products, latent membrane protein-1 (LMP-1) is thought to be the only oncoprotein playing an essential role in cell transformation as well as tumor metastasis. In this study, we tested the effect of suppressing LMP-1 by RNA interference (RNAi) on the proliferative and metastatic potentials of an EBV-positive NPC cell line, C666. We showed that stably suppressing LMP-1 by short hairpin RNA (shRNA) plasmid significantly altered cell motility, substratum adhesion, and transmembrane invasion ability. However, it has little effect on the rate of cell growth and cell cycle control. These results demonstrated the effectiveness of RNAi in suppressing LMP-1, supporting an important role of LMP-1 in NPC metastasis, and suggested a potential application of RNAi-mediated therapeutic strategy for EBV-related NPC.
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http://dx.doi.org/10.1016/j.bbrc.2004.01.045 | DOI Listing |
PLoS Pathog
September 2024
Department of Pediatrics and Adolescent Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Epstein-Barr virus (EBV) manipulates the ubiquitin-proteasome system and regulators of Bcl-2 family to enable the persistence of the virus and survival of the host cells through the expression of viral proteins in distinct latency patterns. We postulate that the combination of bortezomib (proteasome inhibitor) and venetoclax (Bcl-2 inhibitor) [bort/venetoclax] will cause synergistic killing of post-transplant lymphoproliferative disorder (PTLD) through targeting the pro-survival function of latent viral proteins such as latent membrane protein-1 (LMP-1) and EBV nuclear antigen-3C (EBNA-3C). Bort/venetoclax could synergistically kill spontaneous lymphoblastoid cell lines (sLCLs) derived from patients with PTLD and EBV-associated hemophagocytic lymphohistiocytosis by inducing DNA damage response, apoptosis and G1-S cell cycle arrest in a ROS-dependent manner.
View Article and Find Full Text PDFExp Ther Med
January 2022
Department of Orthopedics, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Osteoarthritis (OA) is a common degenerative disease that is associated with the degradation of articular cartilage. Accumulating evidence has confirmed that LIM mineralization protein-1 (LMP-1) is an important agent of bone formation and has been shown to be osteoinductive in various types of disease. However, the underlying mechanisms of LMP-1 in the pathogenesis of OA remain unknown.
View Article and Find Full Text PDFmBio
December 2021
HIV and AIDS Malignancy Branch, National Cancer Institutegrid.48336.3a, National Institutes of Health, Bethesda, Maryland, USA.
Oncogenic gammaherpesviruses express viral products during latent and lytic infection that block the innate immune response. Previously, we found that Kaposi's sarcoma herpesvirus (KSHV/human herpesvirus-8) viral microRNAs (miRNAs) downregulate cholesterol biogenesis, and we hypothesized that this prevents the production of 25-hydroxycholesterol (25HC), a cholesterol derivative. 25HC blocks KSHV infection of primary endothelial cells at a postentry step and decreases viral gene expression of LANA (latency-associated nuclear antigen) and RTA.
View Article and Find Full Text PDFBMC Cancer
June 2021
Division of Morphological Pathology, Department of Basic Laboratory Sciences, School of Health Sciences, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan.
Background: Low-risk human papillomavirus (HPV), such as types 6 and 11, is considered non-oncogenic, but these types have been detected in oral cancer tissue samples, suggesting their possible involvement in oral carcinogenesis. Because double infection of high-risk HPV and Epstein-Barr virus (EBV) is known to be involved in oral carcinogenesis, we hypothesized that low-risk HPV and EBV co-infection can transform the oral cells. To verify our hypothesis, we evaluated the transformation activity of cell lines expressing both low-risk HPV E6/E7 and EBV LMP-1.
View Article and Find Full Text PDFOxid Med Cell Longev
September 2021
Department of Emergency, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, Zhengzhou City, Henan 450052, China.
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