Brusco, Teresa (2024) The Long non-coding MIR205HG promotes prostate cancer stem cell phenotype. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | The Long non-coding MIR205HG promotes prostate cancer stem cell phenotype |
| Autori: | Autore Email Brusco, Teresa teresa.brusco@unina.it |
| Data: | 4 Marzo 2024 |
| Numero di pagine: | 67 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Molecolare e Biotecnologie Mediche |
| Dottorato: | Medicina molecolare e biotecnologie mediche |
| Ciclo di dottorato: | 36 |
| Coordinatore del Corso di dottorato: | nome email Santoro, Massimo massimo.santoro@unina.it |
| Tutor: | nome email Mallardo, Massimo [non definito] |
| Data: | 4 Marzo 2024 |
| Numero di pagine: | 67 |
| Parole chiave: | MIR205HG; LncRNA; ALDH; stemness; CSC; Bcl-XL; DSB |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare Area 05 - Scienze biologiche > BIO/13 - Biologia applicata |
| Depositato il: | 20 Mar 2024 13:56 |
| Ultima modifica: | 12 Ago 2026 05:36 |
| URI: | https://www.fedoa.unina.it/id/eprint/15560 |
Abstract
Prostate cancer (PC) is one of the most common cancers in men. The disease progresses from intraepithelial neoplasia (PIN) to metastatic cancer. Although most of the mechanisms involved in metastasis development are not well understood, recent evidences suggest that Cancer Stem Cells (CSCs) may play a central role. CSCs are a small subpopulation of the tumor with capabilities of self-renewal, differentiation,and tumorigenicity when transplanted into an animal host. In addition, long non-coding (lnc)-RNAs are emerging as inducers or inhibitors of self-renewal, metastasis and invasion of CSCs and it has been shown that their up- or down-regulation can have functional implications for the self-renewal capacity of CSCs. Several cell surface markers such as CD44, CD24 and CD133 and high expression of Aldehyde dehydrogenase(ALDH)isoforms, are commonly used to identify and isolate CSCs. The differential expression of ALDH levels allowed us to isolate two subpopulation (ALDH+ and ALDH-) from prostate bone metastasis cell line (PC3) by cell sorting. RNA-sequencing on ALDH+ vs ALDH- PC3 revealed differences in the transcriptome particularly in lnc-RNAs expression. MicroRNA 205 host gene (MIR205HG) was selected for further analysis due to a significant up-regulation in ALDH+ PC3 cells. PC3 overexpressing MIR205HG isoforms (PC3-MIR205HG3 and PC3-MIR205HG4) displayed an enhanced expression of stemness factors as Nanog, Sox2 and Oct4, a faster wound healing and an increased number and size of tumorspheres. In addition, these cell populations showed chemoresistance and rapid repair to DNA damage. Mechanistically, the two isoforms of MIR205HG interacted with High Mobility Group AT-Hook 2 (HMGA2) protein by promoting its stabilization and cellular localization. It is responsible for many phenotypic and functional features associated with CSCs. Taken together our results suggest a putative role of MIR205HG in promoting prostate CSC phenotype.
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