Piscopo, Fabiola (2025) Novel oncogenic function of OFD1 in cholangiocarcinoma: insights into ciliary dysfunction and tumor growth. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Novel oncogenic function of OFD1 in cholangiocarcinoma: insights into ciliary dysfunction and tumor growth |
| Autori: | Autore Email Piscopo, Fabiola fabiola.piscopo@gmail.com |
| Data: | 9 Febbraio 2025 |
| Numero di pagine: | 69 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Scienze Mediche Traslazionali |
| Dottorato: | Medicina clinica e sperimentale |
| Ciclo di dottorato: | 37 |
| Coordinatore del Corso di dottorato: | nome email Beguinot, Francesco beguino@unina.it |
| Tutor: | nome email Franco, Brunella [non definito] |
| Data: | 9 Febbraio 2025 |
| Numero di pagine: | 69 |
| Parole chiave: | Cholangiocarcinoma; OFD1; Primary cilium |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare Area 05 - Scienze biologiche > BIO/18 - Genetica Area 06 - Scienze mediche > MED/03 - Genetica medica Area 06 - Scienze mediche > MED/06 - Oncologia medica |
| Informazioni aggiuntive: | Ciclo 37 |
| Depositato il: | 17 Ott 2025 14:44 |
| Ultima modifica: | 12 Ago 2026 05:38 |
| URI: | https://www.fedoa.unina.it/id/eprint/16678 |
Abstract
Cholangiocarcinoma (CCA) is a highly lethal malignancy arising from the transformation of cholangiocytes, the epithelial cells lining the biliary ducts. CCA is a rare and aggressive cancer comprising distinct subsets of biliary tumors different in histopathology and molecular alterations. Over recent decades, epidemiological trends have revealed increasing incidence and mortality rates worldwide. Diagnosis at late stages together with frequent emergence of chemoresistance contribute to the persistently poor prognosis of CCA patients. The primary cilium is a solitary, non-motile, microtubule-based organelle extending from the surface of most epithelial cells. Defects in ciliary structure and/or function have been identified as etiological factors underlying ciliopathies, multisystem disorders characterized by extensive genetic heterogeneity and a wide spectrum of phenotypes affecting multiple organs. In addition to its structural role, the primary cilium functions as a critical signaling hub. Moreover, emerging evidence support its involvement in cancer development and progression. In this work, we analyzed the transcriptome of a cohort of CCA patients, identifying the OFD1 gene as one of the most upregulated transcripts. Through in vitro experiments, we demonstrated that OFD1 modulation significantly impacts cell proliferation and migration in both human healthy cholangiocytes and CCA cell lines by influencing several cancer-related signaling pathways. Preliminary data further suggested a correlation between OFD1 expression and patient prognosis. These findings propose ciliary genes, particularly OFD1, as potential biomarkers for improving the clinical management of CCA patients and provide novel insights into the role of primary cilia in cancer biology.
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