Biology subjects

Pinna, L.

Publications and source records attributed to Pinna, L..

3 recordsLinked to original sources

bioRxiv2023

Propionate reinforces epithelial identity and reduces aggressiveness of non-small cell lung carcinoma via chromatin remodelling

Epithelial to mesenchymal transition (EMT) is a developmental cellular program driving metastasis and chemo-resistance in cancer, but its pharmacological treatment has been so far challenging. Targeting deregulated metabolic processes in cancer is emerging as a realistic therapeutic strategy. Here, we used an EMT-focussed integrative functional genomic approach and identified negative association of the short-chain fatty acids propionate and butanoate with EMT in non-small cell lung cancer (NSCLC) patients. Strikingly, in vitro treatment of lung cancer cell lines with propionate reinforced the epithelial transcriptional program promoting cell adhesion and reverting the aggressive and chemoresistant EMT phenotype. Propionate treatment reduced cells metastatic ability in nude mice and limited lymph nodal spread in a genetic NSCLC mouse model. Further analyses indicated chromatin remodeling via H3K27 acetylation (p300-mediated) as the mechanism shifting the EMT balance towards epithelial state upon propionate. Propionate administration could be tested in the clinic for reducing NSCLC aggressiveness. HighlightsAn EMT-centric investigation of metabolic processes in a comprehensive lung cancer transcriptome profiles identified negative associations between EMT and SCFAs (propionate and butyrate) Propionate enhances the epithelial features both at the molecular and cellular levels Pre-treatment of cells with propionate inhibits EMT associated processes including migration and sensitizes the cells to chemotherapeutic drug cisplatin Oral administration of propionate inhibits EMT-mediated lung colonization ability of NSCLC cells, and lymph node metastasis in a genetic mouse NSCLC model Molecular mechanistic investigation of propionate revealed chromatin remodelling through p300-mediated histone acetylation in E-cadherin gene regulation along with epithelial features reinforcement

cancer biology↗

bioRxiv2022

First Detection of Epizootic Haemorrhagic Disease virus in the European Union, Italy-2022.

We describe the first detection in the European Union of the epizootic haemorrhagic disease virus (EHDV). EHDV-8 has been detected in cattle farms in Sardinia and Sicily. The virus has a direct Northern African origin as its genome is identical (>99.9% nucleotide sequence identity) to EHDV-8 strains detected in Tunisia in 2021/2022.

microbiology↗

bioRxiv2021

Metabolic breakdown of non-small cell lung cancers by mitochondrial HSPD1 targeting

The identification of novel targets is of paramount importance to develop more effective drugs and improve the treatment of non-small cell lung cancer (NSCLC), the leading cause of cancer-related deaths worldwide. Since cells alter their metabolic rewiring during tumorigenesis and along cancer progression, targeting key metabolic players and metabolism-associated proteins represents a valuable approach with a high therapeutic potential. Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures. Here, we show HSPD1 (HSP60) as a survival gene ubiquitously expressed in NSCLC and associated with poor patients prognosis. HSPD1 knockdown or its chemical disruption by the small molecule KHS101 induces a drastic breakdown of oxidative phosphorylation, and suppresses cell proliferation both in vitro and in vivo. By combining drug profiling with transcriptomics and through a whole-genome CRISPR/Cas9 screen, we demonstrate that HSPD1-targeted anti-cancer effects are dependent on OXPHOS and validated molecular determinants of KHS101 sensitivity, in particular, the creatine-transporter SLC6A8 and the subunit of the cytochrome c oxidase complex COX5B. These results highlight mitochondrial metabolism as an attractive target and HSPD1 as a potential theranostic marker for developing therapies to combat NCSLC. SignificanceHSPD1 elimination or disruption interferes with NSCLC metabolic activity causing a strong OXPHOS-dependent energetic breakdown, which the cancer cells fail to overcome, highlighting HSPD1 as a potential theranostic marker for improving lung cancer therapy.

cancer biology↗