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. In breast cancer, several lncRNAs were identified and demonstrated to have either oncogenic or tumor-suppressive roles. The functional understanding of the mechanisms of lncRNA action in this disease could represent a potential for translational applications, as these molecules may serve as novel biomarkers of clinical use and potential therapeutic targets. This review highlights the relationship between lncRNAs and the principal hallmark of the luminal breast cancer phenotype, estrogen receptor α (ERα), providing an overview of new potential ways to inhibit estrogenic signaling via this nuclear receptor toward escaping resistance to endocrine therapy.

Identification of functional pathways and molecular signatures in neuroendocrine neoplasms by multi-omics analysis.

BACKGROUND: Neuroendocrine neoplasms (NENs) represent a heterogeneous class of rare tumors with increasing incidence. They are characterized by the ability to secrete peptide hormones and biogenic amines but other reliable biomarkers are lacking, making diagnosis and identification of the primary site very challenging. While in some NENs, such as the pancreatic ones, next generation sequencing technologies allowed the identification of new molecular hallmarks, our knowledge of the molecular profile of NENs from other anatomical sites is still poor. METHODS: Starting from the concept that NENs from different organs may be clinically and genetically correlated, we applied a multi-omics approach by combining multigene panel testing, CGH-array, transcriptome and miRNome profiling and computational analyses, with the aim to highlight common molecular and functional signatures of gastroenteropancreatic (GEP)-NENs and medullary thyroid carcinomas (MTCs) that could aid diagnosis, prognosis and therapy. RESULTS: By comparing genomic and transcriptional profiles, ATM-dependent signaling emerged among the most significant pathways at multiple levels, involving gene variations and miRNA-mediated regulation, thus representing a novel putative druggable pathway in these cancer types. Moreover, a set of circulating miRNAs was also selected as possible diagnostic/prognostic biomarkers useful for clinical management of NENs. CONCLUSIONS: These findings depict a complex molecular and functional landscape of NENs, shedding light on novel therapeutic targets and disease biomarkers to be exploited.

Dynamics of nasopharyngeal tract phageome and association with disease severity and age of patients during three waves of COVID-19.

In December 2019, several patients were hospitalized and diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which subsequently led to a global pandemic. To date, there are no studies evaluating the relationship between the respiratory phageome and the SARS-CoV-2 infection. The current study investigated the phageome profiles in the nasopharyngeal swabs collected from 55 patients during the three different waves of coronavirus disease 2019 (COVID-19) in the Campania Region (Southern Italy). Data obtained from the taxonomic profiling show that phage families belonging to the order Caudovirales have a high abundance in the patient samples. Moreover, the severity of the COVID-19 infection seems to be correlated with the phage abundance.