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postgraduate thesis: An analysis of long non-coding RNA LINC02207 transcript variants in systemic lupus erythematosus
Title | An analysis of long non-coding RNA LINC02207 transcript variants in systemic lupus erythematosus |
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Authors | |
Issue Date | 2022 |
Publisher | The University of Hong Kong (Pokfulam, Hong Kong) |
Citation | Wang Siqi, [王思淇]. (2022). An analysis of long non-coding RNA LINC02207 transcript variants in systemic lupus erythematosus. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. |
Abstract | Introduction: Systemic lupus erythematosus (SLE) is known as an immune
complex-mediated disease with multi-organ involvement and diverse clinical
presentations. Its pathogenesis depends on genetic, immune and environmental
factors, while involving multiple cell types. The heterogeneity of the disease makes
it difficult to diagnose, treat and monitor in the past years. Recently, long noncoding
RNA (lncRNA) was found to be involved in immune dysregulation in
rheumatic diseases, especially SLE. With this new direction, I would like to explore
whether lncRNA could bring new insight into the pathogenesis of SLE, as well as
its significance in aiding clinical diagnosis. Our laboratory previously showed that
LINC02207 gene (LINC2) was overexpressed in SLE neutrophils. In the current
study, the aim is to further investigate the role of various LINC02207 transcript
variants in mediating neutrophil dysfunction in SLE.
Method: The study includes three main aims. (1) Identification and validation of
LINC2 transcript variants relevant to the local population by polymerase chain
reaction (PCR) for the full length of target transcript variants and Sanger
sequencing confirmation. (2) Demonstration of differential expression of LINC2
transcript variants in the neutrophils between normal controls (NC), lupus patients with lupus nephritis (LN patient) and lupus patients without lupus nephritis (NLN
patients) by reverse transcription-quantitative PCR. After that, evaluate the clinical
significance of LINC2 transcript variants in terms of diagnosis and prediction of
clinical outcomes by correlating the expression level of LINC2 transcript variants
to SLE status, nephritis status and selected clinical and laboratory parameters. (3)
Evaluation of the role of LINC2 transcript variants in SLE by correlation with
expression of neutrophil-associated cytokine and cytokine receptors, and to look
for the effect of overexpression of those transcript variants on neutrophil-like cell
line.
Results: The expression levels of all three transcript variants in neutrophils showed
significant upregulation in SLE group when compared with NC group. However,
only LINC2-226 were upregulated in LN group when compared with NLN group.
No significant correlation between the expression level of transcript variants with
SLE disease activity index (SLEDAI) or laboratory parameters were found.
Although the expression level of 3 transcript variants were positively correlated
with IL18, IL18R1, IL18RAP and IL1R1 mRNAs, those mRNAs were not
upregulated upon the overexpression of the 3 transcript variants in the differentiated
HL-60 cell line.
Conclusion: Three transcript variants of LINC02207, namely LINC2-226, LINC2-
217 and LINC2-229, were verified in the neutrophils of the local population. Their
differential expression in SLE patients and their correlation with IL18, IL18R1,
IL18RAP and IL1R1 mRNAs levels in primary neutrophils were identified.
Although their function in neutrophils are still not identified in the overexpression
study, further improvements may yield more definitive results.
|
Degree | Master of Research in Medicine |
Subject | Non-coding RNA Systemic lupus erythematosus |
Dept/Program | Medicine |
Persistent Identifier | http://hdl.handle.net/10722/314661 |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wang Siqi | - |
dc.contributor.author | 王思淇 | - |
dc.date.accessioned | 2022-07-22T06:48:20Z | - |
dc.date.available | 2022-07-22T06:48:20Z | - |
dc.date.issued | 2022 | - |
dc.identifier.citation | Wang Siqi, [王思淇]. (2022). An analysis of long non-coding RNA LINC02207 transcript variants in systemic lupus erythematosus. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. | - |
dc.identifier.uri | http://hdl.handle.net/10722/314661 | - |
dc.description.abstract | Introduction: Systemic lupus erythematosus (SLE) is known as an immune complex-mediated disease with multi-organ involvement and diverse clinical presentations. Its pathogenesis depends on genetic, immune and environmental factors, while involving multiple cell types. The heterogeneity of the disease makes it difficult to diagnose, treat and monitor in the past years. Recently, long noncoding RNA (lncRNA) was found to be involved in immune dysregulation in rheumatic diseases, especially SLE. With this new direction, I would like to explore whether lncRNA could bring new insight into the pathogenesis of SLE, as well as its significance in aiding clinical diagnosis. Our laboratory previously showed that LINC02207 gene (LINC2) was overexpressed in SLE neutrophils. In the current study, the aim is to further investigate the role of various LINC02207 transcript variants in mediating neutrophil dysfunction in SLE. Method: The study includes three main aims. (1) Identification and validation of LINC2 transcript variants relevant to the local population by polymerase chain reaction (PCR) for the full length of target transcript variants and Sanger sequencing confirmation. (2) Demonstration of differential expression of LINC2 transcript variants in the neutrophils between normal controls (NC), lupus patients with lupus nephritis (LN patient) and lupus patients without lupus nephritis (NLN patients) by reverse transcription-quantitative PCR. After that, evaluate the clinical significance of LINC2 transcript variants in terms of diagnosis and prediction of clinical outcomes by correlating the expression level of LINC2 transcript variants to SLE status, nephritis status and selected clinical and laboratory parameters. (3) Evaluation of the role of LINC2 transcript variants in SLE by correlation with expression of neutrophil-associated cytokine and cytokine receptors, and to look for the effect of overexpression of those transcript variants on neutrophil-like cell line. Results: The expression levels of all three transcript variants in neutrophils showed significant upregulation in SLE group when compared with NC group. However, only LINC2-226 were upregulated in LN group when compared with NLN group. No significant correlation between the expression level of transcript variants with SLE disease activity index (SLEDAI) or laboratory parameters were found. Although the expression level of 3 transcript variants were positively correlated with IL18, IL18R1, IL18RAP and IL1R1 mRNAs, those mRNAs were not upregulated upon the overexpression of the 3 transcript variants in the differentiated HL-60 cell line. Conclusion: Three transcript variants of LINC02207, namely LINC2-226, LINC2- 217 and LINC2-229, were verified in the neutrophils of the local population. Their differential expression in SLE patients and their correlation with IL18, IL18R1, IL18RAP and IL1R1 mRNAs levels in primary neutrophils were identified. Although their function in neutrophils are still not identified in the overexpression study, further improvements may yield more definitive results. | - |
dc.language | eng | - |
dc.publisher | The University of Hong Kong (Pokfulam, Hong Kong) | - |
dc.relation.ispartof | HKU Theses Online (HKUTO) | - |
dc.rights | The author retains all proprietary rights, (such as patent rights) and the right to use in future works. | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject.lcsh | Non-coding RNA | - |
dc.subject.lcsh | Systemic lupus erythematosus | - |
dc.title | An analysis of long non-coding RNA LINC02207 transcript variants in systemic lupus erythematosus | - |
dc.type | PG_Thesis | - |
dc.description.thesisname | Master of Research in Medicine | - |
dc.description.thesislevel | Master | - |
dc.description.thesisdiscipline | Medicine | - |
dc.description.nature | published_or_final_version | - |
dc.date.hkucongregation | 2022 | - |
dc.identifier.mmsid | 991044566903603414 | - |