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postgraduate thesis: A comparative study of circulating microRNAs in nasopharyngeal carcinoma patients

TitleA comparative study of circulating microRNAs in nasopharyngeal carcinoma patients
Authors
Advisors
Advisor(s):Wong, STSWei, WI
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Man, O. [萬安瑩]. (2012). A comparative study of circulating microRNAs in nasopharyngeal carcinoma patients. (Unpublished thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4786983.
AbstractNasopharyngeal carcinoma (NPC) is squamous cell carcinoma derived from the epithelial layer of nasopharynx. The incidence is high in Southern China and South-east Asia. In Hong Kong, the prevalent of NPC subtype is undifferentiated NPC and is in close association with Epstein-Barr virus (EBV). MicroRNAs (miRNAs) are small non-coding RNAs. They play vital roles in regulating gene expression at post-transcriptional level. EBV also expresses viral miRNAs but the function remains unclear. In NPC diagnosis and monitoring, circulating EBV DNA level has been commonly used. However, in some cases, EBV DNA is below the detection threshold in the plasma of NPC patients making it impossible to be used in continuous monitoring of the patients. This study aimed to evaluate whether miRNAs (both NPC-derived and EBV-derived miRNAs) could be used as candidate circulating markers for disease monitoring. Candidate gene approach was used to select suitable circulating miRNA markers for NPC patients. Four candidate miRNAs including miR-21, miR-1301, miRBART7 and miR-BART22 were examined. The expression levels were first validated in paired NPC tissues and normal counterparts. Furthermore, circulating miRNA levels were evaluated in the plasma of NPC and normal individuals. To examine the changes of miRNA in response to radiotherapy, changes of circulating miRNA were monitored in 13 NPC patients before and after radiotherapy. In addition, functional assay in cell proliferation was performed to validate the potential role of the candidate miRNA in the pathogenesis of undifferentiated NPC. Of the 4 candidate miRNAs, miR-BART7 was consistently over-expressed in both tumor tissues and plasma samples of NPC. In addition, circulating miRBART7 was also detected in NPC patients in case of the plasma EBV DNA levels below the detection threshold. In response to radiotherapy, 10 of 13 (76.92%) patients had decreasing circulating miR-BART7 in the plasma samples collected at 3 month after radiotherapy. Furthermore, introducing miR-BART7 mimics into the undifferentiated NPC cell line HONE1 and normal nasopharyngeal-derived epithelial cell cultures NP69 and NP460 resulted in significant increases in cell proliferation rates of all the 3 cell lines. To summarize, miR-BART7 expression was significantly higher in NPC patients as a potential oncogenic miRNA. Evaluating the miR-BART7 levels is a possible screening approach in NPC diagnosis and post-treatment monitoring. The oncogenic role of miR-BART7 in the development of undifferentiated NPC deserves further investigation.
DegreeMaster of Philosophy
SubjectSmall interfering RNA.
Nasopharynx - Cancer - Genetic aspects.
Dept/ProgramSurgery

 

DC FieldValueLanguage
dc.contributor.advisorWong, STS-
dc.contributor.advisorWei, WI-
dc.contributor.authorMan, On-ying.-
dc.contributor.author萬安瑩.-
dc.date.issued2012-
dc.identifier.citationMan, O. [萬安瑩]. (2012). A comparative study of circulating microRNAs in nasopharyngeal carcinoma patients. (Unpublished thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4786983.-
dc.description.abstractNasopharyngeal carcinoma (NPC) is squamous cell carcinoma derived from the epithelial layer of nasopharynx. The incidence is high in Southern China and South-east Asia. In Hong Kong, the prevalent of NPC subtype is undifferentiated NPC and is in close association with Epstein-Barr virus (EBV). MicroRNAs (miRNAs) are small non-coding RNAs. They play vital roles in regulating gene expression at post-transcriptional level. EBV also expresses viral miRNAs but the function remains unclear. In NPC diagnosis and monitoring, circulating EBV DNA level has been commonly used. However, in some cases, EBV DNA is below the detection threshold in the plasma of NPC patients making it impossible to be used in continuous monitoring of the patients. This study aimed to evaluate whether miRNAs (both NPC-derived and EBV-derived miRNAs) could be used as candidate circulating markers for disease monitoring. Candidate gene approach was used to select suitable circulating miRNA markers for NPC patients. Four candidate miRNAs including miR-21, miR-1301, miRBART7 and miR-BART22 were examined. The expression levels were first validated in paired NPC tissues and normal counterparts. Furthermore, circulating miRNA levels were evaluated in the plasma of NPC and normal individuals. To examine the changes of miRNA in response to radiotherapy, changes of circulating miRNA were monitored in 13 NPC patients before and after radiotherapy. In addition, functional assay in cell proliferation was performed to validate the potential role of the candidate miRNA in the pathogenesis of undifferentiated NPC. Of the 4 candidate miRNAs, miR-BART7 was consistently over-expressed in both tumor tissues and plasma samples of NPC. In addition, circulating miRBART7 was also detected in NPC patients in case of the plasma EBV DNA levels below the detection threshold. In response to radiotherapy, 10 of 13 (76.92%) patients had decreasing circulating miR-BART7 in the plasma samples collected at 3 month after radiotherapy. Furthermore, introducing miR-BART7 mimics into the undifferentiated NPC cell line HONE1 and normal nasopharyngeal-derived epithelial cell cultures NP69 and NP460 resulted in significant increases in cell proliferation rates of all the 3 cell lines. To summarize, miR-BART7 expression was significantly higher in NPC patients as a potential oncogenic miRNA. Evaluating the miR-BART7 levels is a possible screening approach in NPC diagnosis and post-treatment monitoring. The oncogenic role of miR-BART7 in the development of undifferentiated NPC deserves further investigation.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B47869835-
dc.subject.lcshSmall interfering RNA.-
dc.subject.lcshNasopharynx - Cancer - Genetic aspects.-
dc.titleA comparative study of circulating microRNAs in nasopharyngeal carcinoma patients-
dc.typePG_Thesis-
dc.identifier.hkulb4786983-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineSurgery-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4786983-
dc.date.hkucongregation2012-

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