Nasopharyngeal 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. / published_or_final_version / Surgery / Master / Master of Philosophy
| Identifer | oai:union.ndltd.org:HKU/oai:hub.hku.hk:10722/161543 |
| Date | January 2012 |
| Creators | Man, On-ying., 萬安瑩. |
| Contributors | Wong, STS, Wei, WI |
| Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
| Source Sets | Hong Kong University Theses |
| Language | English |
| Detected Language | English |
| Type | PG_Thesis |
| Source | http://hub.hku.hk/bib/B47869835 |
| Rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works., Creative Commons: Attribution 3.0 Hong Kong License |
| Relation | HKU Theses Online (HKUTO) |
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