LCM-RNAseq Highlights Intratumor Heterogeneity and a lncRNA Signature from Archival Tissues of GH-Secreting PitNETs.

Background: This study explores the potential for hidden variations within seemingly uniform regions of growth hormone-secreting pituitary neuroendocrine tumors (GH-PitNETs). We employed archived tissue samples using Laser Capture Microdissection Sequencing (LCM-RNAseq) to probe the molecular landscape of these tumors at a deeper level.

Methods: A customized protocol was developed to extract, process, and sequence small amounts of RNA from formalin-fixed, paraffin-embedded (FFPE) tissues derived from five patients with GH-secreting PitNETs and long-term follow-up (≥10 years).

The COVID-19 legacy: consequences for the human DNA methylome and therapeutic perspectives.

The COVID-19 pandemic has left a lasting legacy on human health, extending beyond the acute phase of infection. This article explores the evidence suggesting that SARS-CoV-2 infection can induce persistent epigenetic modifications, particularly in DNA methylation patterns, with potential long-term consequences for individuals' health and aging trajectories. The review discusses the potential of DNA methylation-based biomarkers, such as epigenetic clocks, to identify individuals at risk for accelerated aging and tailor personalized interventions.

Prognostic Impact of H19/Cell Adhesion Molecules Circuitry on Prostate Cancer Biopsy.

Introduction: Metastatic prostate cancer (PCa) presents a significant challenge in oncology due to its high mortality rate and the absence of effective biomarkers for predicting patient outcomes. Building on previous research that highlighted the critical role of the long noncoding RNA (lncRNA) H19 and cell adhesion molecules in promoting tumor progression under hypoxia and estrogen stimulation, this study aimed to assess the potential of these components as prognostic biomarkers for PCa at the biopsy stage.

Methods: This research utilized immunohistochemistry and droplet digital PCR to analyze formalin-fixed paraffin-embedded (FFPE) biopsies, focusing on specific markers within the H19/cell adhesion molecules pathway.

High fat diet affects the hippocampal expression of miRNAs targeting brain plasticity-related genes.

Metabolic disorders such as insulin resistance and type 2 diabetes are associated with brain dysfunction and cognitive deficits, although the underpinning molecular mechanisms remain elusive. Epigenetic factors, such as non-coding RNAs, have been reported to mediate the molecular effects of nutrient-related signals. Here, we investigated the changes of miRNA expression profile in the hippocampus of a well-established experimental model of metabolic disease induced by high fat diet (HFD).

Targeting of H19/cell adhesion molecules circuitry by GSK-J4 epidrug inhibits metastatic progression in prostate cancer.

Background: About 30% of Prostate cancer (PCa) patients progress to metastatic PCa that remains largely incurable. This evidence underlines the need for the development of innovative therapies. In this direction, the potential research focus might be on long non-coding RNAs (lncRNAs) like H19, which serve critical biological functions and show significant dysregulation in cancer.

How epigenetics impacts on human diseases.

Epigenetics is a rapidly growing field of biology that studies the changes in gene expression that are not due to alterations in the DNA sequence but rather the chemical modifications of DNA and its associated proteins. Epigenetic mechanisms can profoundly influence gene expression, cell differentiation, tissue development, and disease susceptibility. Understanding epigenetic changes is essential to elucidate the mechanisms underlying the increasingly recognized role of environmental and lifestyle factors in health and disease and the intergenerational transmission of phenotypes.

MALAT1 as a Regulator of the Androgen-Dependent Choline Kinase A Gene in the Metabolic Rewiring of Prostate Cancer.

Background: Choline kinase alpha (CHKA), an essential gene in phospholipid metabolism, is among the modulated MALAT1-targeted transcripts in advanced and metastatic prostate cancer (PCa).

Methods: We analyzed CHKA mRNA by qPCR upon MALAT1 targeting in PCa cells, which is characterized by high dose-responsiveness to the androgen receptor (AR) and its variants. Metabolome analysis of MALAT1-depleted cells was performed by quantitative High-resolution 1 H-Nuclear Magnetic Resonance (NMR) spectroscopy.

Hippocampal Estrogen Signaling Mediates Sex Differences in Retroactive Interference.

Despite being a crucial physiological function of the brain, the mechanisms underlying forgetting are still poorly understood. Estrogens play a critical role in different brain functions, including memory. However, the effects of sex hormones on forgetting vulnerabilitymediated by retroactive interference (RI), a phenomenon in which newly acquired information interferes with the retrieval of already stored information, are still poorly understood.

Metabolic Reprogramming by Malat1 Depletion in Prostate Cancer.

The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes growth and progression in prostate cancer (PCa); however, little is known about its possible impact in PCa metabolism. The aim of this work has been the assessment of the metabolic reprogramming associated with MALAT1 silencing in human PCa cells and in an ex vivo model of organotypic slice cultures (OSCs). Cultured cells and OSCs derived from primary tumors were transfected with MALAT1 specific gapmers.

Somatic Deletion in Exon 10 of Aryl Hydrocarbon Receptor Gene in Human GH-Secreting Pituitary Tumors.

Objective/purpose: The aryl hydrocarbon receptor (AHR) pathway plays a critical role in the biology of Growth Hormone (GH)-secreting pituitary tumor (somatotropinoma). Germline rs2066853 variant was found to be more frequent among acromegaly patients and associated with a more severe disease with larger invasive somatropinoma, and with resistance to somatostatin analogs treatment in patients living in polluted areas. However, no somatic changes in gene have been reported so far in acromegaly patients.

CPEB1 orchestrates a fine-tuning of miR-145-5p tumor-suppressive activity on TWIST1 translation in prostate cancer cells.

TWIST1 is a basic helix-loop-helix transcription factor, and one of the master Epithelial-to-Mesenchymal Transition (EMT) regulators. We show that tumor suppressor miR-145-5p controls TWIST1 expression in an immortalized prostate epithelial cell line and in a tumorigenic prostate cancer-derived cell line. Indeed, shRNA-mediated miR-145-5p silencing enhanced TWIST1 expression and induced EMT-associated malignant properties in these cells.

Signaling through estrogen receptors modulates long non-coding RNAs in prostate cancer.

Prostate cancer (PCa) is a sex-steroid hormone-dependent cancer in which estrogens play a critical role in both initiation and progression. Recently, several long non-coding RNAs (lncRNAs) have been associated with PCa and are supposedly playing a pivotal role in the biology and progression of this type of cancer. In this review, we focused on some lncRNAs that are known for their androgen and estrogen transcriptional responsiveness in PCa.

H19-Dependent Transcriptional Regulation of β3 and β4 Integrins Upon Estrogen and Hypoxia Favors Metastatic Potential in Prostate Cancer.

Estrogen and hypoxia promote an aggressive phenotype in prostate cancer (PCa), driving transcription of progression-associated genes. Here, we molecularly dissect the contribution of long non-coding RNA H19 to PCa metastatic potential under combined stimuli, a topic largely uncovered. The effects of estrogen and hypoxia on H19 and cell adhesion molecules' expression were investigated in PCa cells and PCa-derived organotypic slice cultures (OSCs) by qPCR and Western blot.

The Dark That Matters: Long Non-coding RNAs as Master Regulators of Cellular Metabolism in Non-communicable Diseases.

Non-coding RNAs are pivotal for many cellular functions, such as splicing, gene regulation, chromosome structure, and hormone-like activity. Here, we will report about the biology and the general molecular mechanisms associated with long non-coding RNAs (lncRNAs), a class of >200 nucleotides-long ribonucleic acid sequences, and their role in chronic non-transmissible diseases. In particular, we will summarize knowledge about some of the best-characterized lncRNAs, such as H19 and MALAT1, and how they regulate carbohydrate and lipid metabolism as well as protein synthesis and degradation.

Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation.

Inhibitors of Vascular Endothelial Growth Factor target both tumor vasculature and cancer cells that have hijacked VEGF Receptors (VEGFRs) signaling for tumor growth-promoting activities. It is important to get precise insight in the specificity of cell responses to these antiangiogenic drugs to maximize their efficiency and minimize off-target systemic toxicity. Here we report that Axitinib, an inhibitor of VEGFRs currently in use as a second line treatment for advanced renal cell carcinoma, promotes senescence of human endothelial cells in vitro.