Non-coding RNA profiling in BRAF-mutant cutaneous melanoma before and after Spry1 depletion.

Cutaneous melanoma (CM), with a continuously rising incidence worldwide, represents the most aggressive type of skin cancer, and it leads to the majority of skin cancer-related deaths. Approximately 50% of CM carry the activating BRAF mutation and, although BRAF inhibitors have demonstrated clinical efficacy, most patients often develop early resistance to treatment. Aberrant expression of non-coding RNAs (ncRNAs), which represent less than 2% of the entire transcriptome, has been implicated in CM development and progression.

Multi-omics based and AI-driven drug repositioning for epigenetic therapy in female malignancies.

Histone post-translational modifications (PTMs) have long been recognized as critical regulators of chromatin dynamics and gene expression, with aberrations in these processes driving tumorigenesis, immune escape, metastasis, and therapy resistance. While multi-omics technologies are generating ever more detailed maps of the histone landscape, translating these insights into clinical practice remains challenging. The ongoing convergence of high-throughput omics technologies and Artificial Intelligence (AI) is revolutionizing drug repositioning strategies, offering new precision tools to identify histone-targeted therapies for solid tumors.

BRPF1 inhibition reduces migration and invasion of metastatic ovarian cancer cells, representing a potential therapeutic target.

Ovarian Cancer (OC) is the most lethal gynecological malignancy, characterized by peritoneal metastasis, directly linked to most OC-related deaths. Here, by interrogating CRISPR-Cas9 loss-of-function genetic screen data, we identified a list of genes essential for metastatic OC, including several well-known oncogenes (PAX8, CCNE1, WWTR1, WT1, KAT6A, MECOM, and SOX17) and others whose roles in OC have not yet been explored. Protein-protein interaction analysis of the selected genes revealed the presence of a protein network participating in the epigenetic regulation of gene expression.

Suppression of Spry1 reduces HIF1α-dependent glycolysis and impairs angiogenesis in BRAF-mutant cutaneous melanoma.

Background: About 50% of cutaneous melanoma (CM) harbors the activating BRAF mutation which exerts most of the oncogenic effects through the MAPK signaling pathway. In the last years, a number of MAPK modulators have been identified, including Spry1. In this context, we have recently demonstrated that knockout of Spry1 (Spry1) in BRAF-mutant CM led to cell cycle arrest and apoptosis, repressed cell proliferation in vitro, and reduced tumor growth in vivo.

LncRNA PVT1 links estrogen receptor alpha and the polycomb repressive complex 2 in suppression of pro-apoptotic genes in hormone-responsive breast cancer.

RNA-based therapeutics highlighted novel approaches to target either coding or noncoding molecules for multiple diseases treatment. In breast cancer (BC), a multitude of deregulated long noncoding RNAs (lncRNAs) have been identified as potential therapeutic targets also in the context of antiestrogen resistance, and the RNA binding activity of the estrogen receptor α (ERα) points additional potential candidates to interfere with estrogenic signaling. A set of lncRNAs was selected among ERα-associated RNAs in BC cell nuclei due to their roles in processes such as transcriptional regulation and epigenetic chromatin modifications.

Does gut microbiota dysbiosis impact the metabolic alterations of hydrogen sulfide and lanthionine in patients with chronic kidney disease?

Background: Chronic Kidney Disease (CKD) is characterized by a methionine-related metabolic disorder involving reduced plasma levels of hydrogen sulfide (HS) and increased lanthionine. The gut microbiota influences methionine metabolism, potentially impacting sulfur metabolite dysfunctions in CKD. We evaluated whether gut microbiota dysbiosis contributes to HS and lanthionine metabolic alterations in CKD.

Essential gene screening identifies the bromodomain-containing protein BRPF1 as a new actionable target for endocrine therapy-resistant breast cancers.

Identifying master epigenetic factors controlling proliferation and survival of cancer cells allows to discover new molecular targets exploitable to overcome resistance to current pharmacological regimens. In breast cancer (BC), resistance to endocrine therapy (ET) arises from aberrant Estrogen Receptor alpha (ERα) signaling caused by genetic and epigenetic events still mainly unknown. Targeting key upstream components of the ERα pathway provides a way to interfere with estrogen signaling in cancer cells independently from any other downstream event.

Influence of Mycobiota in the Nasopharyngeal Tract of COVID-19 Patients.

The nasopharyngeal tract contains a complex microbial community essential to maintaining host homeostasis. Recent studies have shown that SARS-CoV-2 infection changes the microbial composition of the nasopharynx. Still, little is known about how it affects the fungal microbiome, which could provide valuable insights into disease pathogenesis.

Small non-coding RNA transcriptomic profiling in adult and fetal human brain.

Small non-coding RNAs (sncRNAs) make up ~1% of the transcriptome; nevertheless, they play significant roles in regulating cellular processes. Given the complexity of the central nervous system, sncRNAs likely hold particular importance in the human brain. In this study, we provide sncRNA transcriptomic profiles in a range of adult and prenatal brain regions, with a focus on piRNAs, due to their underexplored expression in somatic cells and tissue-specific nature.

Transcriptome analysis of macrophages during Brucella abortus infection clarifies the survival mechanisms of the bacteria.

Brucellosis is a critical zoonotic disease impacting humans and animals globally, causing symptoms like fever and arthritis in humans and reproductive issues in animals. The disease stems from the Brucella genus, adept at evading the immune system and proliferating within host cells. This study explores how Brucella abortus manipulates host cellular mechanisms to sustain infection, focusing on the interaction with murine macrophages over 24 h.

Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors.

Introduction: About 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR).

Downregulation of praja2 restrains endocytosis and boosts tyrosine kinase receptors in kidney cancer.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer in the adult population. Late diagnosis, resistance to therapeutics and recurrence of metastatic lesions account for the highest mortality rate among kidney cancer patients. Identifying novel biomarkers for early cancer detection and elucidating the mechanisms underlying ccRCC will provide clues to treat this aggressive malignant tumor.

Glucose Deprivation Promotes Pseudohypoxia and Dedifferentiation in Lung Adenocarcinoma.

Unlabelled: Increased utilization of glucose is a hallmark of cancer. Sodium-glucose transporter 2 (SGLT2) is a critical player in glucose uptake in early-stage and well-differentiated lung adenocarcinoma (LUAD). SGLT2 inhibitors, which are FDA approved for diabetes, heart failure, and kidney disease, have been shown to significantly delay LUAD development and prolong survival in murine models and in retrospective studies in diabetic patients, suggesting that they may be repurposed for lung cancer.

RIZ2 at the crossroad of the EGF/EGFR signaling in colorectal cancer.

Background: Colorectal cancer (CRC) is the third most deadly and fourth most diagnosed cancer worldwide. Despite the progress in early diagnosis and advanced therapeutic options, CRC shows a poor prognosis with a 5 year survival rate of ~ 45%. PRDM2/RIZ, a member of PR/SET domain family (PRDM), expresses two main molecular variants, the PR-plus isoform (RIZ1) and the PR-minus (RIZ2).

Autophagy in BRAF-mutant cutaneous melanoma: recent advances and therapeutic perspective.

Macroautophagy, hereafter referred to as autophagy, represents a highly conserved catabolic process that maintains cellular homeostasis. At present, the role of autophagy in cutaneous melanoma (CM) is still controversial, since it appears to be tumor-suppressive at early stages of malignant transformation and cancer-promoting during disease progression. Interestingly, autophagy has been found to be often increased in CM harboring BRAF mutation and to impair the response to targeted therapy.

Host nasopharyngeal transcriptome dataset of a SARS-CoV-2 positive Italian cohort.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has affected millions of people worldwide and has significant implications for public health. Host transcriptomics profiling provides comprehensive understanding of how the virus interacts with host cells and how the host responds to the virus. COVID-19 disease alters the host transcriptome, affecting cellular pathways and key molecular functions.

Metabolic Robustness to Growth Temperature of a Cold- Adapted Marine Bacterium.

Microbial communities experience continuous environmental changes, with temperature fluctuations being the most impacting. This is particularly important considering the ongoing global warming but also in the "simpler" context of seasonal variability of sea-surface temperature. Understanding how microorganisms react at the cellular level can improve our understanding of their possible adaptations to a changing environment.

Glucose deprivation promotes pseudo-hypoxia and de-differentiation in lung adenocarcinoma.

Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction by glucose transporter blockade or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are unknown.

Functional Relationships between Long Non-Coding RNAs and Estrogen Receptor Alpha: A New Frontier in Hormone-Responsive Breast Cancer Management.

In the complex and articulated machinery of the human genome, less than 2% of the transcriptome encodes for proteins, while at least 75% is actively transcribed into non-coding RNAs (ncRNAs). Among the non-coding transcripts, those ≥200 nucleotides long (lncRNAs) are receiving growing attention for their involvement in human diseases, particularly cancer. Genomic studies have revealed the multiplicity of processes, including neoplastic transformation and tumor progression, in which lncRNAs are involved by regulating gene expression at epigenetic, transcriptional, and post-transcriptional levels by mechanism(s) that still need to be clarified.