Exploring the methyl-verse: Dynamic interplay of epigenome and m6A epitranscriptome.

The orchestration of dynamic epigenetic and epitranscriptomic modifications is pivotal for the fine-tuning of gene expression. However, these modifications are traditionally examined independently. Recent compelling studies have disclosed an interesting communication and interplay between m6A RNA methylation (m6A epitranscriptome) and epigenetic modifications, enabling the formation of feedback circuits and cooperative networks.

Characterization of novel ACE2 mRNA transcripts: The potential role of alternative splicing in SARS-CoV-2 infection.

The human angiotensin converting enzyme 2 (ACE2) gene encodes a type I transmembrane protein, which is homologous to angiotensin I-converting enzyme (ACE) and belongs to the angiotensin-converting enzyme family of dipeptidyl carboxypeptidases. As highlighted by the COVID-19 pandemic, ACE2 is not only crucial for the renin-angiotensin-aldosterone system (RAAS), but also displays great affinity with the SARS-CoV-2 spike protein, representing the major receptor of the virus. Given the significance of ACE2 in COVID-19, especially among cancer patients, the present study aims to explore the transcriptional landscape of ACE2 in human cancer and non-cancerous cell lines through the design and implementation of a custom targeted long-read sequencing approach.

Kallikrein-related peptidases: mechanistic understanding for potential therapeutic targeting in cancer.

Introduction: Human kallikrein-related peptidases (KLKs) represent a subgroup of 15 serine endopeptidases involved in various physiological processes and pathologies, including cancer.

Areas Covered: This review aims to provide a comprehensive overview of the KLK family, highlighting their genomic structure, expression profiles and substrate specificity. We explore the role of KLKs in tumorigenesis, emphasizing their potential as biomarkers and therapeutic targets in cancer treatment.

Small non-coding RNAs as diagnostic, prognostic and predictive biomarkers of gynecological cancers: an update.

Introduction: Non-coding RNAs (ncRNAs) comprise a heterogeneous cluster of RNA molecules. Emerging evidence suggests their involvement in various aspects of tumorigenesis, particularly in gynecological malignancies. Notably, ncRNAs have been implicated as mediators within tumor signaling pathways, exerting their influence through interactions with RNA or proteins.

New insights into the dynamics of m6A epitranscriptome: hybrid-seq identifies novel mRNAs of the m6A writers METTL3/14.

N6-methyladenosine (m6A), a prevalent mRNA modification, is dynamically regulated by methyltransferases, including METTL3 and METTL14. In the current study, we employed a custom hybrid-seq method to identify novel / transcripts, explore their protein-coding capacities and predict the putative role of the METTL isoforms. Demultiplexing of the hybrid-seq barcoded datasets unraveled the expression patterns of the newly identified mRNAs in major malignancies as well as in non-malignant cells, providing a deeper understanding of the methylation pathways.

Beyond the Chromosome: Recent Developments in Decoding the Significance of Extrachromosomal Circular DNA (eccDNA) in Human Malignancies.

Extrachromosomal circular DNA (eccDNA) is a form of a circular double-stranded DNA that exists independently of conventional chromosomes. eccDNA exhibits a broad and random distribution across eukaryotic cells and has been associated with tumor-related properties due to its ability to harbor the complete gene information of oncogenes. The complex and multifaceted mechanisms underlying eccDNA formation include pathways such as DNA damage repair, breakage-fusion-bridge (BFB) mechanisms, chromothripsis, and cell apoptosis.

ciRS-7 circular RNA overexpression in plasma cells is a promising molecular biomarker of unfavorable prognosis in multiple myeloma.

Several non-coding RNAs are known to be associated with the pathobiology and progression of multiple myeloma (MM). ciRS-7 (also known as CDR1-AS), a key oncogenic circular RNA (circRNA) that sponges miR-7-5p and other cancer-related microRNAs, was recently found to be downregulated in malignant plasma cells resistant to immunomodulatory drugs. Considering that various circRNAs have a strong potential as molecular biomarkers, we aimed to investigate the expression of ciRS-7 in plasma cell disorders, assess its prognostic importance in MM, and compare these findings with those of individuals with smoldering MM (SMM) and monoclonal gammopathy of unknown significance (MGUS).

Unraveling novel mRNA transcripts of the human DNA N-glycosylase 1 (NTHL1) gene with the implementation of an innovative targeted DNA-seq assay.

The human NTHL1 gene encodes a DNA glycosylase that plays a key role in the base excision repair (BER) pathway, repairing oxidative DNA damage and maintaining genome integrity. The physiological activity of NTHL1 is crucial in preventing genetic alterations that can lead to cancer. In this study, we employed an innovative targeted DNA sequencing (DNA-seq) methodology to explore the transcriptional landscape of the NTHL1 gene, revealing previously uncharacterized alternative splicing events and novel exons.

copy number alteration in bladder cancer: Integrative analysis in patient-derived xenografts and cancer patients.

Bladder cancer (BlCa) is an extensively heterogeneous disease that leads to great variability in tumor evolution scenarios and lifelong patient surveillance, emphasizing the need for modern, minimally invasive precision medicine. Here, we explored the clinical significance of copy number alterations (CNAs) in BlCa. CNA profiling was performed in 15 patient-derived xenografts (PDXs) and validated in The Cancer Genome Atlas BlCa (TCGA-BLCA;  = 408) and Lindgren et al.

Core Promoter Methylation in Pretreatment Cell-Free DNA: A Liquid Biopsy Tool for Muscle-Invasive Bladder Cancer Treatment Outcome.

Purpose: The lack of personalized management of bladder cancer (BlCa) results in patients' lifelong post-treatment monitoring with invasive interventions, underlying the urgent need for tailored and minimally invasive health care services. On the basis of our previous findings on miR-143/145 cluster methylation in bladder tumors, we evaluated its clinical significance in pretreatment cell-free DNA (cfDNA) of patients with BlCa.

Materials And Methods: Methylation analysis was performed in our screening cohort (120 patients with BlCa; 20 age-matched healthy donors) by bisulfite-based pyrosequencing.

Exploring the molecular biomarker utility of circCCT3 in multiple myeloma: A favorable prognostic indicator, particularly for R-ISS II patients.

Circular RNAs (circRNAs) are associated with the pathobiology of multiple myeloma (MM). Recent findings regarding circCCT3 support its involvement in the development and progression of MM, through microRNA sponging. Thus, we aimed to examine the expression of circCCT3 in smoldering and symptomatic MM and to assess its clinical importance.

Small RNA-seq and clinical evaluation of tRNA-derived fragments in multiple myeloma: Loss of mitochondrial i-tRF results in patients' poor treatment outcome.

Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA-derived fragment (tRF) profiles in MM and precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential MM-related tRFs in ameliorating MM prognosis and risk stratification. Small RNA-seq was performed to profile tRFs in bone marrow CD138 plasma cells, revealing the significant deregulation of the mitochondrial internal tRF (mt-i-tRF) in MM versus sMM/MGUS.

Unraveling the Concealed Transcriptomic Landscape of PTEN in Human Malignancies.

Background: Phosphatase and tensin homolog, widely known as PTEN, is a major negative regulator of the PI3K/AKT/mTOR signaling pathway, involved in the regulation of a variety of important cellular processes, including cell proliferation, growth, survival, and metabolism. Since most of the molecules involved in this biological pathway have been described as key regulators in cancer, the study of the corresponding genes at several levels is crucial.

Objective: Although previous studies have elucidated the physiological role of PTEN under normal conditions and its involvement in carcinogenesis and cancer progression, the transcriptional profile of PTEN has been poorly investigated.

Exploring the time-dependent regulatory potential of microRNAs in breast cancer cells treated with proteasome inhibitors.

Purpose: Breast cancer (BrCa) is a predominant type of cancer with a disparate molecular nature. MicroRNAs (miRNAs) have emerged as promising key players in the regulation of pathological processes in BrCa. Proteasome inhibitors (PIs) emerged as promising anticancer agents for several human malignancies, including BrCa, inhibiting the function of the proteasome.

3'-tRF-Cys overexpression in HEK-293 cells alters the global expression profile and modulates cellular processes and pathways.

tRNA fragments (tRFs) are small non-coding RNAs generated through specific cleavage of tRNAs and involved in various biological processes. Among the different types of tRFs, the 3'-tRFs have attracted scientific interest due to their regulatory role in gene expression. In this study, we investigated the role of 3'-tRF-Cys, a tRF deriving from cleavage in the T-loop of tRNA, in the regulation of gene expression in HEK-293 cells.

Discovery and Comprehensive Characterization of Novel Circular RNAs of the Apoptosis-Related Gene in Human Ovarian and Prostate Cancer Cells, Using Nanopore Sequencing.

CircRNAs have become a novel scientific research hotspot, and an increasing number of studies have shed light on their involvement in malignant progression. Prompted by the apparent scientific gap in circRNAs from apoptosis-related genes, such as , we focused on the identification of novel circRNAs in human ovarian and prostate cancer cells. Total RNA was extracted from ovarian and prostate cancer cell lines and reversely transcribed using random hexamer primers.

Next-generation sequencing reveals altered gene expression and enriched pathways in triple-negative breast cancer cells treated with oleuropein and oleocanthal.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis and limited treatment options. Oleuropein and oleocanthal are bioactive chemicals found in extra-virgin olive oil; they have been shown to have anti-cancer potential. In this study, we examined the inhibitory effects of these two natural compounds, on MDA-MB-231 and MDA-MB-468 TNBC cell lines.

Cancer quiescence: non-coding RNAs in the spotlight.

Cancer quiescence reflects the ability of cancer cells to enter a reversible slow-cycling or mitotically dormant state and represents a powerful self-protecting mechanism preventing cancer cell 'damage' from hypoxic conditions, nutrient deprivation, immune surveillance, and (chemo)therapy. When stress conditions are restrained, and tumor microenvironment becomes beneficial, quiescent cancer cells re-enter cell cycle to facilitate tumor spread and cancer progression/metastasis. Recent studies have highlighted the dynamic role of regulatory non-coding RNAs (ncRNAs) in orchestrating cancer quiescence.

Association of high miR-27a, miR-206, and miR-214 expression with poor patient prognosis and increased chemoresistance in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype, associated with early metastasis and recurrence as well as poor patient outcome. TNBC does not or weakly respond to hormonal or HER2-targeted therapies. Therefore, there is a strong need to identify other potential molecular targets for TNBC therapy.

Novel circular RNAs of the apoptosis-related BAX and BCL2L12 genes identified in a chronic lymphocytic leukemia cell line using nanopore sequencing.

Circular RNAs (circRNAs), a novel RNA type generated by back-splicing, are key regulators of gene expression, with deregulated expression and established involvement in leukemia. The products of BCL2 and its homologs, including BAX and BCL2L12, are implicated in chronic lymphocytic leukemia (CLL). However, to the best of our knowledge, nothing is known about circRNAs produced by these two genes and their role in CLL.

Deregulated Expression of in Patients with Bladder Urothelial Cancer: The Diagnostic Potential of the Isoform.

Cellular and molecular immune components play a crucial role in the development and perpetuation of human malignancies, shaping anti-tumor responses. A novel immune regulator is interleukin-37 (IL-37), already shown to be involved in the inflammation associated with the pathophysiology of many human disorders, including cancer. The interplay between tumor and immune cells is of great importance, especially for highly immunogenic tumors such as bladder urothelial carcinoma (BLCA).

Hybrid-seq deciphers the complex transcriptional profile of the human DNA repair associated gene.

Breast Cancer Gene 1 (BRCA1) is a tumour suppressor protein that modulates multiple biological processes including genomic stability and DNA damage repair. Although the main BRCA1 protein is well characterized, further proteomics studies have already identified additional BRCA1 isoforms with lower molecular weights. However, the accurate nucleotide sequence determination of their corresponding mRNAs is still a barrier, mainly due to the increased mRNA length of (~5.