CATALOGO DEI PRODOTTI DELLA RICERCA
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Englishfor mutated forms of p53 protein that cause both a loss of wild-type p53 (wt_p53) function and a gain of pro-tumorigenic features to mutant p53 (mut_p53), so called gain of function (GOF). Several studies demonstrated that mut_p53 GOF promotes tumor invasiveness and metastasis. However, the molecular mechanisms underneath are not fully characterized. Non-coding RNAs, particularly lncRNAs (long non-coding RNAs), are central players of gene regulation including wt_p53 pathway, but up today there are not reports that investigate the role of lncRNAs in the pro-invasive phenotype of mut_p53. Therefore, to better understand the mechanism of mut_p53 oncogenic functions, in this PhD thesis, we aim to investigate whether lncRNAs participate to mut_p53 gain of function, precisely in HGSOC and BC cell models. To do this, we evaluated changes in in vitro invasiveness assays (mesothelial clearance and 3D colony assay) in TP53_silenced HGSOC and BC cell lines. To profile the expression of lncRNAs in TP53_silenced cells, we used a RNA deep-sequencing analysis of nuclear long RNAs. Next, we validated deep-sequencing results in mut_p53 and wt_p53 cell models. We observed that mut_p53 enhances the ability of HGSOC to invade the peritoneum and of basal BC cells to invade extracellular matrix. From NGS data analysis of TP53_silenced cells, we discovered 806 and 1820 lncRNAs differentially expressed in BC and HGSOC cell lines, respectively. Using qRT-PCR, we investigated the 10 gene most differentially expressed both in mut_p53 and wt_p53 cell lines. To sum up, we report a role of mut_p53 both in HGSOC and BC metastatic phenotype, and we identify some lncRNAs (e.g. LINC00704) which could be accountable of this effect. Our future plan is to activate or repress the expression of these candidate genes and evaluate the impact on tumor cell biology.
| Titolo: | LONG NON-CODING RNAs IN CANCER |
| Autori: | |
| Data di pubblicazione: | 2018 |
| Abstract: | for mutated forms of p53 protein that cause both a loss of wild-type p53 (wt_p53) function and a gain of pro-tumorigenic features to mutant p53 (mut_p53), so called gain of function (GOF). Several studies demonstrated that mut_p53 GOF promotes tumor invasiveness and metastasis. However, the molecular mechanisms underneath are not fully characterized. Non-coding RNAs, particularly lncRNAs (long non-coding RNAs), are central players of gene regulation including wt_p53 pathway, but up today there are not reports that investigate the role of lncRNAs in the pro-invasive phenotype of mut_p53. Therefore, to better understand the mechanism of mut_p53 oncogenic functions, in this PhD thesis, we aim to investigate whether lncRNAs participate to mut_p53 gain of function, precisely in HGSOC and BC cell models. To do this, we evaluated changes in in vitro invasiveness assays (mesothelial clearance and 3D colony assay) in TP53_silenced HGSOC and BC cell lines. To profile the expression of lncRNAs in TP53_silenced cells, we used a RNA deep-sequencing analysis of nuclear long RNAs. Next, we validated deep-sequencing results in mut_p53 and wt_p53 cell models. We observed that mut_p53 enhances the ability of HGSOC to invade the peritoneum and of basal BC cells to invade extracellular matrix. From NGS data analysis of TP53_silenced cells, we discovered 806 and 1820 lncRNAs differentially expressed in BC and HGSOC cell lines, respectively. Using qRT-PCR, we investigated the 10 gene most differentially expressed both in mut_p53 and wt_p53 cell lines. To sum up, we report a role of mut_p53 both in HGSOC and BC metastatic phenotype, and we identify some lncRNAs (e.g. LINC00704) which could be accountable of this effect. Our future plan is to activate or repress the expression of these candidate genes and evaluate the impact on tumor cell biology. |
| Handle: | http://hdl.handle.net/11562/979250 |
| Appare nelle tipologie: | 07.13 Doctoral Thesis |
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| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| Michela_Coan_iris.pdf | Tesi di dottorato | Accesso ristretto | Open Access Visualizza/Apri |
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