Die Expression tumorkorrelierter mikroRNAs und ihrer potenziellen Ziel-Gene APAF1 und HMGA2 in Lungenkarzinomen und Lymphknotenmetastasen
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Philipps-Universität Marburg
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Abstract
MiRNAs are single-stranded, non-coding and approximately 22 nucleotide-long RNAs being
able to affect almost all cellular processes such as growth, differentiation and apoptosis, by
translational inhibition or degradation of their target mRNA. They have been increasingly
studied over the last 20 years, as they have been shown in the literature to be valid biomarkers
of a wide variety of diseases including cancer. Lung carcinomas are among the most commonly
diagnosed malignant neoplasms and account for the most cancer-related deaths worldwide.
Despite state-of-the-art therapies, the prognosis of lung cancer is often poor and therefore
requires new concepts for early detection, diagnosis and therapy. MiRNAs offer great potential
in this regard, as many studies have already shown that numerous miRNAs exhibit an altered
expression in lung carcinomas, are involved in carcinogenesis and metastasis, and may
correlate with TNM stage and patient prognosis.
In the present dissertation, the expression of miRNAs miR-19a, miR-19b, miR-21-1, miR-30-5p,
let-7b-5p, and let-7f-5p and their potential targets HMGA2 and APAF1 was investigated in lung
carcinoma and lymph node metastasis compared to healthy tissue. Formalin-fixed and
paraffin-embedded (FFPE) samples from 31 patients operated at the University Hospital of
Marburg between 2000 and 2004 were collected. Twenty-eight lung carcinoma samples, 16
lymph node metastasis samples, 14 healthy lung samples, and 12 healthy lymph node samples
were included in the study. After RNA isolation, four pools were created from the samples,
which contained all samples in the group in equal amounts. The expression of miRNAs and
mRNAs was measured by quantitative real-time reverse transcriptase polymerase chain
reaction.
The expression of miRNAs in lung carcinoma was compared with their expression in healthy
lung tissues. The expression of miRNAs in lymph node metastasis was compared to healthy
lung and lymph node tissue. Hsa-miR-19a and hsa-miR-19b did not show significantly altered
expression in lung cancer tissues. Instead, they showed a strong downregulation in lymph
node metastasis tissues compared to healthy lung and lymph node tissues. The expression of
hsa-miR-30a-5p was unchanged in lung carcinoma tissues. Its expression was down regulated
in lymph node metastasis tissues compared to healthy lung tissues and up regulated compared
to healthy lymph node tissues. Hsa-miR-21-1 showed a strong downregulation in lung
carcinoma samples and a strong upregulation in lymph node metastases compared with
healthy lymph node tissue. Hsa-let-7b-5p exhibited significant downregulation in lung
carcinoma tissues, whereas no altered expression of hsa-let-7f-5p was detected.
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However, both hsa-let-7b-5p and hsa-let-7f-5p showed a significant upregulation in lymph
node metastasis tissues compared to healthy lung and lymph node tissues.
The potential target (of miRNAs hsa-miR-19a, hsa-miR-19b, and hsa-miR-21-1) APAF1 exhibited
a significant downregulation in lung cancer tissues and a significant upregulation in lymph
node tissues. APAF1 did not correlate with any of the predicted miRNAs in lung cancer tissues.
An inverse correlation between APAF1 and hsa-miR-19a and hsa-miR-19b was found in lymph
node metastasis tissues compared to healthy lymph node tissues. The potential target (of
miRNAs hsa-let-7b-5p and hsa-let-7f-5p) HMGA2 was found upregulated in lung cancer tissues
and in lymph node metastasis tissues compared to healthy lung, but its expression was stable
in comparison to healthy lymph node tissues. Thus, it inversely correlated with the expression
of hsa-let-7b-5p in lung carcinoma tissue but not with hsa-let-7f-5p. Because HMGA2 did not
show altered expression in lymph node metastases compared with healthy lymph node, it did
not correlate with either miRNA.
The study performed provides an overview of the expression of miRNAs in lung carcinomas
and in lymph node metastases. The exploration of the expression profiles in primary tumor
and metastasis could provide a better understanding of lung tumorigenesis and metastasis and
enable a better diagnosis and therapy in the future. Further studies will enable to validate the
results presented here and to highlight the miRNA expression profile in lymph node
metastases. Thus providing better insight into the pathogenesis of lung cancer metastasis.
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Dates
Created: 2022Issued: 2022-07-04Updated: 2022-07-04
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
DDC-Numbers
610
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Tieck, Jannis: Die Expression tumorkorrelierter mikroRNAs und ihrer potenziellen Ziel-Gene APAF1 und HMGA2 in Lungenkarzinomen und Lymphknotenmetastasen. : Philipps-Universität Marburg 2022-07-04. DOI: https://doi.org/10.17192/z2022.0273.