Background and Objective: The methylation of Ubiquitin C-Terminal Hydrolase L1 (UCHL1) gene has been reported in many human cancers including nasopharyngeal carcinoma (NPC). In Vietnam, the methylation of UCHL1 gene’s promoter in NPC has not been demonstrated yet. In this study, a systematic literature revision was carried out to summarize the current evidences about the frequencies of UCHL-1 gene’s promoter methylation in NPC for further application in Vietnamese population. Methods: A systematic literature analysis was conducted based on the comprehensive studies. Moreover, many bioinformatic tools such as Methprimer, TFsearch, IDT OligoAnalyzer 3.1 were used to predict the CpG islands, transcriptional factors, and to pick up the MSP (Methylation-Specific PCR) primers. Results: Total of three previous studies were summarized and accessed for eligibility from literature research. As the results, the average weight methylated frequencies were 72.4% and 13.0% for NPC and non-cancerous samples, respectively. The significant association between UCHL-1 promoter methylation and NPC with the OR of 10.459 (95% CI = 4.915 – 22.254, p < 0.001) and RR of 4.117 (95% CI = 1.958 – 6.645, p < 0.0001) based on the random effects model, was observed. Moreover, we were successful in predicting the CpG islands as well as identifying transcriptional factor binding sites which served as “hot spot” for ideal primer pick up and located in gene promoter. Conclusion: The methylation of UCHL-1 gene promoter was significantly associated and contributed to NPC developmentin which it could be further applied in evaluation of UCHL-1 gene promoter status in Vietnamese population.
Nasopharyngeal carcinoma (NPC) is one of the most frequent cancer types in Vietnam, with high mortality rate. Therefore, the early diagnosis and detection of NPC is urgently needed to improve patient survival. Recent studies have confirmed that the infection of Epstein-Barr virus (EBV) and polymorphism in RPMS1 and A73 are considered as the etiological factor associated with NPC. However, in Vietnam, there are no studies relevant to the identification of polymorphism of RMPS1 and A73. With the aims, in future, to develop a technique based on detecting the frequencies of RPMS1 and A73 variants as biomarkers of prognosis and early diagnosis of NPC, we conducted the initial in silico analysis (1) Data collection, statistical analysis the frequencies detection of RPMS1 and A73 variants from various previous published studies; (2) Determine experimental methods to predict and diagnose early NPC and examine necessary steps in silico. As the results, we established the systematic databases of RPMS1 and A73 polymorphism, and evaluation the primer set for the amplification of RPMS1 and A73, which could be applied in further studies related to the identification of RPMS1 and A73 gene polymorphism to find out the potential biomarkers for screening, diagnosis as well as NPC treatment.
miRNA (microRNA) are short RNA molecules in length from 20 to 24 nucleotides that have been shown to play an important role in regulating gene expression in many different types of human cancer. Meanwhile, miRNA-214 is one of the known miRNAs involved in the formation of nasopharyngeal carcinoma (NPC) through overexpression that promotes proliferation and development of cancer cells. However, in Vietnam, the study of miR-214 related to NPC has not been conducted yet. With the aims to develop the further studies of miR-214 on NPC in Vietnamese patients, in this initial study, we conducted the analysis of miR-214 expression in previous publications, as well as the prediction of miR-214 potential target genes, which involved in many cellular pathways. Here we applied bioinformatics tools to predict miRNAs and their targets, and discuss the role of miR-214 in the context of human cancers. As the results, miR-214 acted as the oncogenic roles in NPC, relevanted to many pathways, such as cell proliferation, apoptosis, metastasis and invasion through the its target genes LTF, Bim, Bax, LINC0086, etc. In conclusion, the use of computional approaches facilitate the further experimental validation of miRNAs in general, particularly miR-214, in Vietnamese NPC patients.
Benchwarmer (BNCH) gene encodes an orphan transmembrane transporter belonging to the Major Facilitator Superfamily (MFS), facilitating the transport of ions, amino acids, simple sugars and recently lysolipids. The loss of BNCH function caused lethality in several animal models with neurodegeneration and senescence. At the cellular level, dysregulation of BNCH leads to adverse phenotypes of lysosome and also autophagy (i.e. dyshomeostasis, accumulation of carbohydrates and sphingolipids, and enlarged lysosome). However, the molecular function and ligand of BNCH protein remain to be unrevealed. This study aims to create a radical substitution change in human BNCH coding gene to knock out the protein functions. More specifically, lysine (K) was used to replace the glutamic acid residue 164 (E164K) which is conserved in many animals (fly, zebrafish, mouse and human) and this E164K mutation recapitulated BNCH mutant phenotype. In conclusion, BNCH harboring E164K (BNCH*) was successfully produced by site-directed mutagenesis and cloned into pcDNA.3.1 vector. The construct was transformed into E. coli OmniMAX and that provides a valuable cell assay to search for the molecular ligand of BNCH.
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