| Abstract |
Despite the great advances in cancer research, lung cancer still remains the number one killer type
of cancer worldwide, mainly due to lack of efficiency in early diagnosis. Typically, lung cancer bears
both genetic and epigenetic abnormalities. Non-coding RNAs (ncRNAs) are epigenetic regulators
frequently distorted in cancer. The aim of this project was dual: to examine the expression profile of
previously identified targets and to perform a microarray-based profiling of lung cancer samples.
We assessed hsa-miR-7150 expression in Non Small Cell Lung Cancer (NSCLC). No difference in the
levels of hsa-miR-7150 expression between tumour and normal samples was detected. However,
hsa-miR-7150 expression was associated with histology (p=0.006) and tumour stage (p=0.038). We
also investigated EGFR (Epidermal Growth Factor Receptor) mRNA expression in lung cancer and its
potential regulation by 2 lncRNAs (LOC102723622 and EGFR-AS1) located within the EGFR locus. The
expression of EGFR, EGFR-AS1 and LOC102723622 was assessed by real time qPCR in lung tumour
and adjacent normal tissue samples. In addition, we analyzed the methylation status of EGFR gene
promoter by bisulfite pyrosequencing. Only LOC102723622 showed significant elevated expression
in tumours compared to normal lung tissue (median fold change = 3.5, p=0.019). Expression of EGFR
was correlated to EGFR-AS1 expression (Rho=0.43, p=0.005). EGFR promoter was unmethylated in
both tumour and normal tissues. Finally, we constructed a lncRNA microarray experiment. Analysis
of the results pointed out some promising lncRNA biomarker candidates for further validation.
Overall, in this study we clarified that hsa-miR-7150 is not an ideal biomarker for lung cancer.
Moreover, for the first time we analysed the methylation status of EGFR promoter and
demonstrated a unique potential epigenetic regulation of EGFR through an intragenic lncRNA.
However, the significance of LOC102723622 overexpression must be further investigated to
ascertain its functional importance in lung cancer development.
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Epigenetic deregulation in lung cancer
