eEF2K is a poor prognostic factor and novel molecular target in pancreatic cancer: regulating tumor growth and progression via the tumor microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with an average survival time of only six months following diagnosis, even with currently available therapies. Thus, PDAC represents a significant therapeutic challenge, necessitating a deeper understanding of its biology and tumor microenvironment (TME) to develop more effective treatments and improve patient outcomes. Here, we report that the expression of Eukaryotic Elongation Factor-2 Kinase (eEF2K) is associated with shorter patient survival and demonstrate that eEF2K signaling is critical for the PDAC tumor growth and regulated by the TME.

The mutational landscape and functional effects of noncoding ultraconserved elements in human cancers.

The mutational landscape of phylogenetically ultraconserved elements (UCEs), especially those in noncoding DNAs (ncUCEs), and their functional relevance in cancers remain poorly characterized. Here, we perform a systematic analysis of whole-genome and in-house targeted UCE sequencing datasets from more than 3000 patients with cancer of 13,736 UCEs and demonstrate that ncUCE somatic alterations are common. Using a multiplexed CRISPR knockout screen in colorectal cancer cells, we show that the loss of several altered ncUCEs significantly affects cell proliferation.

Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state.

Inhibition of microRNA-660-5p decreases breast cancer progression through direct targeting of TMEM41B.

Background: Breast cancer is the most prevalent cancer among women worldwide. Most breast cancer-related deaths result from metastasis and drug resistance. Novel therapies are imperative for targeting metastatic and drug-resistant breast cancer cells.

The DLEU2/miR-15a/miR-16-1 cluster shapes the immune microenvironment of chronic lymphocytic leukemia.

The development and progression of chronic lymphocytic leukemia (CLL) depend on genetic abnormalities and on the immunosuppressive microenvironment. We have explored the possibility that genetic drivers might be responsible for the immune cell dysregulation that shapes the protumor microenvironment. We performed a transcriptome analysis of coding and non-coding RNAs (ncRNAs) during leukemia progression in the Rag2γ MEC1-based xenotransplantation model.

MicroRNA-1307-3p contributes to breast cancer progression through PRM2.

Background: Despite advances in screening and therapy, breast cancer (BC) remains the predominant cancer in women globally. Dysregulation of microRNAs (miRNAs) is pivotal in carcinogenesis across various cancers, including BC. Evidence indicates that miR-1307-3p is upregulated in BC tumors, yet its target genes are not fully elucidated.

miRNA Biology in Chronic Lymphocytic Leukemia.

microRNAs (miRNAs) are a class of small non-coding RNAs that play a crucial regulatory role in fundamental biological processes and have been implicated in various diseases, including cancer. The first evidence of the cancer-related function of miRNAs was discovered in chronic lymphocytic leukemia (CLL) in the early 2000s. Alterations in miRNA expression have since been shown to strongly influence the clinical course, prognosis, and response to treatment in patients with CLL.

miR-142: A Master Regulator in Hematological Malignancies and Therapeutic Opportunities.

MicroRNAs (miRNAs) are a type of non-coding RNA whose dysregulation is frequently associated with the onset and progression of human cancers. miR-142, an ultra-conserved miRNA with both active -3p and -5p mature strands and wide-ranging physiological targets, has been the subject of countless studies over the years. Due to its preferential expression in hematopoietic cells, miR-142 has been found to be associated with numerous types of lymphomas and leukemias.

Non-coding RNAs in disease: from mechanisms to therapeutics.

Non-coding RNAs (ncRNAs) are a heterogeneous group of transcripts that, by definition, are not translated into proteins. Since their discovery, ncRNAs have emerged as important regulators of multiple biological functions across a range of cell types and tissues, and their dysregulation has been implicated in disease. Notably, much research has focused on the link between microRNAs (miRNAs) and human cancers, although other ncRNAs, such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are also emerging as relevant contributors to human disease.

Anti-miR-93-5p therapy prolongs sepsis survival by restoring the peripheral immune response.

Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to a lack of insight into deep mechanistic processes. In the past decade, deciphering the functions of small noncoding miRNAs in sepsis pathogenesis became a dynamic research topic.

17β-estradiol promotes extracellular vesicle release and selective miRNA loading in ERα-positive breast cancer.

The causes and consequences of abnormal biogenesis of extracellular vesicles (EVs) are not yet well understood in malignancies, including in breast cancers (BCs). Given the hormonal signaling dependence of estrogen receptor-positive (ER+) BC, we hypothesized that 17β-estradiol (estrogen) might influence EV production and microRNA (miRNA) loading. We report that physiological doses of 17β-estradiol promote EV secretion specifically from ER+ BC cells via inhibition of miR-149-5p, hindering its regulatory activity on SP1, a transcription factor that regulates the EV biogenesis factor nSMase2.

Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update.

Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics.

Risk of uterine niche following single-layer locked versus unlocked uterine closure: a randomized study.

Introduction: The primary objective of the present study is to evaluate the effect of single-layer locked versus single-layer unlocked uterine closure techniques on the development of uterine niche. The secondary objective is to evaluate the effect of the ratio of lower uterine segment (LUS) to upper uterine segment (UUS) on the development of uterine niche, which was not previously investigated in literature but which the authors consider to be a major risk factor for the development of uterine niche.

Methods: Included in this randomized study were 194 patients who were admitted to the Department of Obstetrics and Gynecology at Health Sciences University Antalya Training and Research Hospital and who underwent cesarean section (CS) due to any reason between October 2017 and May 2018.

A novel lncRNA derived from an ultraconserved region: lnc-, a potential biomarker in luminal A breast cancer.

The human genome contains 481 ultraconserved regions (UCRs), which are genomic stretches of over 200 base pairs conserved among human, rat, and mouse. The majority of these regions are transcriptionally active (T-UCRs), and several have been found to be differentially expressed in tumours. Some T-UCRs have been functionally characterized, but of those few have been associated to breast cancer (BC).

ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer.

Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion.

The Long Noncoding RNA CCAT2 Induces Chromosomal Instability Through BOP1-AURKB Signaling.

Background & Aims: Chromosomal instability (CIN) is a carcinogenesis event that promotes metastasis and resistance to therapy by unclear mechanisms. Expression of the colon cancer-associated transcript 2 gene (CCAT2), which encodes a long noncoding RNA (lncRNA), associates with CIN, but little is known about how CCAT2 lncRNA regulates this cancer enabling characteristic.

Methods: We performed cytogenetic analysis of colorectal cancer (CRC) cell lines (HCT116, KM12C/SM, and HT29) overexpressing CCAT2 and colon organoids from C57BL/6N mice with the CCAT2 transgene and without (controls).

The Interplay between MicroRNAs and the Components of the Tumor Microenvironment in B-Cell Malignancies.

An increased focus is being placed on the tumorigenesis and contexture of tumor microenvironment in hematopoietic and solid tumors. Despite recent clinical revolutions in adoptive T-cell transfer approaches and immune checkpoint blockade, tumor microenvironment is a major obstacle to tumor regression in B-cell malignancies. A transcriptional alteration of coding and non-coding RNAs, such as microRNAs (miRNAs), has been widely demonstrated in the tumor microenvironment of B-cell malignancies.

Therapeutic potential of FLANC, a novel primate-specific long non-coding RNA in colorectal cancer.

Objective: To investigate the function of a novel primate-specific long non-coding RNA (lncRNA), named FLANC, based on its genomic location (co-localised with a pyknon motif), and to characterise its potential as a biomarker and therapeutic target.

Design: FLANC expression was analysed in 349 tumours from four cohorts and correlated to clinical data. In a series of multiple in vitro and in vivo models and molecular analyses, we characterised the fundamental biological roles of this lncRNA.

miR-543 regulates the epigenetic landscape of myelofibrosis by targeting TET1 and TET2.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by cytopenia and extramedullary hematopoiesis, resulting in splenomegaly. Multiple pathological mechanisms (e.g.