Lung cancer is the most common cause of cancer deaths worldwide. Major advances in the understanding of the molecular pathogenesis of lung cancer may lead to new strategies for early detection, diagnosis, staging and therapy that hold promise for improving lung cancer outcomes. MicroRNAs (miRNAs) are 19 to 25 nucleotide-long non-coding RNAs that regulate gene expression by binding complementary sequences of target mRNAs. Many studies have reported that alterations in miRNA expression are involved in the development of several human tumours. MicroRNAs could also constitute a new class of blood-based biomarkers useful for cancer detection and prognosis definition. Moreover, miRNAs released in the bloodstream can also have a role in targeting tumour cells promoting growth and invasiveness. The intent of this project is to characterize tissue and plasmatic miRNA expression of early lung cancer patients, and to assess their functional role in lung carcinogenesis. Low Dose Computed Tomography (LDCT) detected lung tumours and paired normal lung tissues were first profiled for miRNAs expression. In particular we found miRNAs associated with clinic-pathological characteristics in both tumour and normal lung tissue. Plasma samples from the same patients were compared with those of disease-free individuals. Specific diagnostic and prognostic miRNA signatures, composed by 24 miRNAs, were defined in plasma samples of lung cancer patients collected before and at the time of disease detection. To understand if circulating miRNAs have a functional role in tumour development, their activity was assessed in lung tumour and normal bronchial epithelial cells. Preliminary results suggested that miR-486~5p and miR-660 act as tumour suppressor miRNAs, while miR-197 and miR-28-3p behave as oncogenic miRNAs. Overall, miRNA profiling and related functional studies would provide greater knowledge of the regulatory events underlying the development and progression of lung cancer and lead to the identification of new therapeutic targets for this malignancy.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:607485 |
| Date | January 2013 |
| Creators | Boeri, Mattia |
| Publisher | Open University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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