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HOTTIP Predicts Poor Survival in Gastric Cancer Patients and Contributes to Cisplatin Resistance by Sponging miR-216a-5p.

Gastric cancer (GC) is a significant public health burden worldwide, and cisplatin resistance is the leading cause for the failure of chemotherapy in this disease. Previous studies have revealed that HOXA transcript at the distal tip (HOTTIP) is involved in the pathology of GC and is associated with poor overall survival. However, the functional role of HOTTIP in GC chemoresistance remains unclear. In this study, quantitative real-time PCR was used to analyze HOTTIP expression in GC cell lines and in tissues of GC patients who received cisplatin-based chemotherapy. The mechanism of HOTTIP-medi

Knockdown of LINC00963 targets miR-1252-5p to reduce inflammatory levels and ECM degradation in nucleus pulposus cells of IDD.

BACKGROUND: In middle-aged and older adults, intervertebral disc degeneration (IDD) is a major cause of chronic low back pain and disability. This pathological process is closely linked to the activation of inflammatory factors resulting from an imbalance in extracellular matrix (ECM) metabolism and abnormalities in Nucleus pulposus cells (NPCs). This study aims to clarify the functional importance of LINC00963 in IDD and its potential molecular mechanisms. METHODS: 102 IDD patients and 88 scoliosis controls were enrolled. IL-1β-stimulated NPCs modeled IDD in vitro. RT-qPCR detected LINC00963,

PRMT5: An Emerging Target for Pancreatic Adenocarcinoma.

The overall survival of pancreatic ductal adenocarcinoma (PDAC) remains poor and its incidence is rising. Targetable mutations in PDAC are rare, thus novel therapeutic approaches are needed. Protein arginine methyltransferase 5 (PRMT5) overexpression is associated with worse survival and inhibition of PRMT5 results in decreased cancer growth across multiple cancers, including PDAC. Emerging evidence also suggests that altered RNA processing is a driver in PDAC tumorigenesis and creates a partial dependency on this process. PRMT5 inhibition induces altered splicing and this vulnerability can be

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… There are examples where both PRMTs similarly regulate a common substrate, such as SPT5, modifying its interaction with RNA polymerase II [ 141 ]. … Methylation of SPT5 Regulates Its Interaction with RNA Polymerase II and Transcriptional Elongation Properties Mol. Cell 2003 11 1055 1066 10.1016/S1097-2765(03)00101-1 12718890 142. Reintjes A. Fuchs J.E. Kremser L. Lindner H.H. Liedl K.R. Huber L.A. Valovka T. …

Future Options of Molecular-Targeted Therapy in Small Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide. With a focus on histology, there are two major subtypes: Non-small cell lung cancer (NSCLC) (the more frequent subtype), and small cell lung cancer (SCLC) (the more aggressive one). Even though SCLC, in general, is a chemosensitive malignancy, relapses following induction therapy are frequent. The standard of care treatment of SCLC consists of platinum-based chemotherapy in combination with etoposide that is subsequently enhanced by PD-L1-inhibiting atezolizumab in the extensive-stage disease, as the addition of immune-checkp

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… Other Transcription Inhibitors in SCLC Lurbinectedin, a selective inhibitor of trans-activated RNA polymerase II transcription, was tested in SCLC. … Due to a reasonable side-effect profile, selective inhibitors of trans-activated RNA polymerase II might harbor potential in SCLC first-line treatment. 2.2.3. Notch2/3 Inhibition in SCLC Besides Notch1 tumor suppressor function in SCLC, Notch2 and Notch3 have oncogenic potential in SCLC [ 149 ]. …

Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016.

Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

Novel roles of PIWI proteins and PIWI-interacting RNAs in human health and diseases.

Non-coding RNA has aroused great research interest recently, they play a wide range of biological functions, such as regulating cell cycle, cell proliferation, and intracellular substance metabolism. Piwi-interacting RNAs (piRNAs) are emerging small non-coding RNAs that are 24-31 nucleotides in length. Previous studies on piRNAs were mainly limited to evaluating the binding to the PIWI protein family to play the biological role. However, recent studies have shed more lights on piRNA functions; aberrant piRNAs play unique roles in many human diseases, including diverse lethal cancers. Therefore

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… polymerase II (Pol II) into long noncoding transcripts and piRNA precursors in the nucleus and then enter the cytoplasm for further processing and modification [ 36 ]. … Abbreviations Piwi-interacting RNAs RNA-induced silencing complex RNA polymerase II Histone H3 Lys9 Heterochromatin protein 1 Rhino-Deadlock-Cutoff TATA box-binding protein-associated Factor 2 Flamenco Aubergine Argonaute 3 Zucchini Armitage Transposable element Cytosine phospho-guanine …

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

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… Indirect regulation modes include: NR signaling pathways may compete for overlapping DNA-binding sites; NR heterodimer partners may cause redistribution or squelching; Components of the transcriptional machinery, such as RNA polymerase II (Pol II) and transcriptional coregulators, may cause redistribution … Indirect regulation modes include: NR signaling pathways may compete for overlapping DNA-binding sites; NR heterodimer partners may cause redistribution or squelching; Components of the transcriptional machinery, such as RNA polymerase II (Pol II) and transcriptional coregulators, may cause redistribution …

Canine Gastric Cancer: Current Treatment Approaches.

Human gastric cancer (GC) ranks as the fifth most prevalent cancer worldwide, and is the third leading cause of cancer-related death. The incidence of GC is lower in dogs than in humans, accounting for less than 1% of all canine malignancies. In recent years, efforts have been made to understand the pathogenesis of GC and in find an appropriate therapy to maximize curative results, such as adjuvant chemotherapy treatments in addition to surgery. Although surgery is the first-line treatment, it is associated with several complications. In terms of chemotherapeutic intervention, canine gastric c

Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pa

BET bromodomain protein inhibition is a therapeutic option for medulloblastoma.

Medulloblastoma is the most common malignant brain tumor of childhood, and represents a significant clinical challenge in pediatric oncology, since overall survival currently remains under 70%. Patients with tumors overexpressing MYC or harboring a MYC oncogene amplification have an extremely poor prognosis. Pharmacologically inhibiting MYC expression may, thus, have clinical utility given its pathogenetic role in medulloblastoma. Recent studies using the selective small molecule BET inhibitor, JQ1, have identified BET bromodomain proteins, especially BRD4, as epigenetic regulatory factors for

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… Through its interaction with BRD4, P-TEFb is recruited to promoters to phosphorylate the carboxy-terminal domain of the large subunit of RNA polymerase II. … Elongation by RNA polymerase II: the short and long of it. Genes & development. 2004;18(20):2437–2468. doi: 10.1101/gad.1235904. 16. Yang Z, He N, Zhou Q. Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. …

Anticancer natural products from the Middle East and North Africa: biodiversity, mechanisms, and translational challenges.

Cancer remains one of the leading causes of morbidity and mortality worldwide, imposing substantial clinical, societal, and economic burdens. Despite major advances in surgical oncology, systemic chemotherapy, radiation therapy, molecularly targeted therapeutics, and immune checkpoint inhibition, contemporary cancer treatment remains constrained by dose-limiting toxicities, intratumoral and intertumoral heterogeneity, and the inexorable emergence of multifaceted drug resistance mechanisms. These persistent therapeutic challenges have reinstated interest in natural products (NPs) as evolutionar

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… Its anticancer activity also extends to transcriptional suppression via RNA polymerase II inhibition and MYC downregulation, reflecting a broader polypharmacological profile ( 105 ). … Its mechanism extends beyond direct DNA damage to include inhibition of activated transcription through RNA polymerase II interaction and degradation, modulation of tumor microenvironment through effects on tumor-associated macrophages, and displacement of oncogenic transcription factors from target …

Nucleic acid aptamers in orthopedic diseases: promising therapeutic agents for bone disorders.

Precision medicine has become a cornerstone in modern therapeutic strategies, with nucleic acid aptamers emerging as pivotal tools due to their unique properties. These oligonucleotide fragments, selected through the Systematic Evolution of Ligands by Exponential Enrichment process, exhibit high affinity and specificity toward their targets, such as DNA, RNA, proteins, and other biomolecules. Nucleic acid aptamers offer significant advantages over traditional therapeutic agents, including superior biological stability, minimal immunogenicity, and the capacity for universal chemical modificatio

Ameloblastoma RNA profiling uncovers a distinct non-coding RNA signature.

Ameloblastoma of the jaws remains the top difficult to treat odontogenic tumour and has a high recurrence rate. New evidence suggests that non-coding RNAs (ncRNAs) play a critical role in tumourgenesis and prognosis of cancer. However, ameloblastoma ncRNA expression data is lacking. Here we present the first report of ameloblastoma ncRNA signatures. A total of 95 ameloblastoma cases and a global array transcriptome technology covering > 285.000 full-length transcripts were used in this two-step analysis. The analysis first identified in a test cohort 31 upregulated ameloblastoma-associated ncR

Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.

Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet the body's demand for synthesis of biological macromolecules such as proteins and nucleic acids. However, in the process of tumor development, the nitrogen metabolism of tumor cells is reprogrammed to meet the demand of rapid proliferation, showing significantly different metabolic characteristics from normal cells. Key enzymes in the tumor microenvironment affect nitrogen meta

Application of the CRISPR/Cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer.

The 2020 Nobel Prize in Chemistry was awarded to Emmanuelle Charpentier and Jennifer Doudna for the development of the Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease9 (CRISPR/Cas9) gene editing technology that provided new tools for precise gene editing. It is possible to target any genomic locus virtually using only a complex nuclease protein with short RNA as a site-specific endonuclease. Since cancer is caused by genomic changes in tumor cells, CRISPR/Cas9 can be used in the field of cancer research to edit genomes for exploration of the mechanisms of t

Functions and Therapeutic Potentials of Long Noncoding RNA in Skeletal Muscle Atrophy and Dystrophy.

Skeletal muscle is the most abundant tissue in the human body and is responsible for movement, metabolism, energy production and longevity. Muscle atrophy is a frequent complication of several diseases and occurs when protein degradation exceeds protein synthesis. Genetics, ageing, nerve injury, weightlessness, cancer, chronic diseases, the accumulation of metabolic byproducts and other stimuli can lead to muscle atrophy. Muscular dystrophy is a neuromuscular disorder, part of which is caused by the deficiency of dystrophin protein and is mostly related to genetics. Muscle atrophy and muscular

Role of Exosomal Non-Coding RNAs in Bone-Related Diseases.

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and "package" non-coding RNAs and "deliver" them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are invol

Изменения в профилях нейтрофильных мРНК в множестве склерозов и идентификации потенциальных генов для дальнейшего исследования.

ВВЕДЕНИЕ: Множественный склероз (MS) является хроническим и изнурительным воспалительным заболеванием центральной нервной системы (КНС), характеризующимся демиэлированием и нейродегенерацией. Появляющиеся данные свидетельствуют о наличии нейтрофилов в патогенезе MS, особенно в рамках таких процессов, как образование нейтрофильных внеклеточных ловушек (NETs) и дегрануляция, которые могут усилить воспаление и автонепроницаемость. МЕТОДЫ: Секвенирование последовательности периферийных нейтрофилов крови у пациентов с синдромом MS и здоровый контроль выявили дифференциально выраженные гены (DEGs).

Mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable