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A high mortality rate was found in cancer patients with distant metastasis. Development of targeted drugs for effectively inhibiting cancer metastasis is the key for increasing therapeutic success. In the current study, a folding paper system was developed to mimic a tumor–vascular interface for the study of long-distance cell migration. Correlation between the cell migration distance and metastasis-associated gene was successfully analyzed by disassembling the stacked paper construct. The result revealed that the migration distance and number of migrated cells were highly correlated to cell characteristics. Moreover, immunocytochemistry was directly conducted on the paper layer to study the signaling pathway. Kelch-like and protein tyrosine phosphatase families were examined and the PTPN13 gene was shown to regulate long-distance cell migration. By analyzing the phosphorylated mTOR, the PTPN13 gene was further confirmed to be a tumor suppressor gene that inhibits long-distance cell migration. The folding paper system provides an alternative approach for long-distance cell migration. Metastasis-associated gene expression can be analyzed to potentially develop targeted drugs for cancer metastasis inhibition. [ABSTRACT FROM AUTHOR]

Recent studies have revealed the importance of multiple microRNAs (miRNAs) in promoting tumorigenesis, among which mir-17-92/Oncomir-1 exhibits potent oncogenic activity. Genomic amplification and elevated expression of mir-17-92 occur in several human B-cell lymphomas, and enforced mir-17-92 expression in mice cooperates with c-myc to promote the formation of B-cell lymphomas. Unlike classic protein-coding oncogenes, mir-17-92 has an unconventional gene structure, where one primary transcript yields six individual miRNAs. Here, we functionally dissected the individual components of mir-17-92 by assaying their tumorigenic potential in vivo. Using the Eμ1/4-myc model of mouse B-cell lymphoma, we identified miR-19 as the key oncogenic component of mir-17-92, both necessary and sufficient for promoting c-myc-induced lymphomagenesis by repressing apoptosis. The oncogenic activity of miR-19 is at least in part due to its repression of the tumor suppressor Pten. Consistently, miR-19 activates the Akt?"mTOR (mammalian target of rapamycin) pathway, thereby functionally antagonizing Pten to promote cell survival. Our findings reveal the essential role of miR-19 in mediating the oncogenic activity of mir-17-92, and implicate the functional diversity of mir-17-92 components as the molecular basis for its pleiotropic effects during tumorigenesis. [ABSTRACT FROM AUTHOR]

Objective: To provide a comprehensive overview of the current knowledge structure and research hotspots of Cowden syndrome via bibliometrics. Methods: The articles and reviews related to Cowden syndrome were included from the Web of Science Core Collection (WoSCC) database. VOSviewer, CiteSpace and GraphPad Prism were used to conduct the bibliometric analysis. Results: The number of papers focusing on Cowden syndrome was relatively low initially but increased rapidly from 1997 to 1999, and then maintained small-scale fluctuation. A total of 1,557 papers from 65 countries/regions and 1,762 institutions were identified. The USA was the most productive country, and Ohio State University was the most productive institution. In terms of the number of publications, Human Molecular Genetics ranked first, and Cancer Research was the most frequently cited journal. Eng was the most productive author, and Liaw was the most co-cited author. Phosphatase and tensin homologue (PTEN), germline mutations, gene, cancer, mutations, tumour suppressor gene and breast were high-frequency key words in this field. Conclusion: This study was the first comprehensive bibliometric overview of the current state and development of Cowden disease. The mutation of PTEN and associated cancers, especially breast, thyroid and endometrial cancer, could be the focus of future research in this field. [ABSTRACT FROM AUTHOR]

Humans have generally evolved some adaptations to protect against UV and different levels of background ionizing radiation. Similarly, elephants and whales have evolved adaptations to protect against cancer, such as multiple copies of the tumor suppressor gene p53, due to their large size and long lifespan. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Humans living in regions with high levels of background radiation, e.g. in Ramsar, Iran where exposure rates exceed those on the surface of Mars, seem to have developed some kind of protection against the ionizing radiation. However, humans in general have not developed cancer-fighting adaptations, so they instead rely on medical technologies and interventions. The difference in cancer protection strategies between humans and elephants/whales depends on genetics, lifestyle, environmental exposures, and evolutionary pressures. In this paper, we discuss how the differences in evolutionary adaptations between humans and elephants could explain why elephants have evolved a protective mechanism against cancer, whereas humans have not. Studying elephant adaptations may provide insights into new cancer prevention and treatment strategies for humans, but further research is required to fully understand the evolutionary disparities. [ABSTRACT FROM AUTHOR]

Oncogenesis is a complex and multi-step process, controlled by several factors including epigenetic modifications. It is considered that histone modifications are critical components in the regulation of gene expression, protein functions, and molecular interactions. Dysregulated post-translationally modified histones and the related enzymatic systems are key players in the control of cell proliferation and differentiation, which are associated with the onset and progression of cancers. The most of traditional investigations on cancer have focused on mutations of oncogenes and tumor suppressor genes. However, increasing evidence indicates that epigenetics, especially histone post-translational modifications (PTMs) play important roles in various cancer types. Mass spectrometry-based proteomic approaches have demonstrated tremendous potential in PTMs profiling and quantitation in different biological systems. In this paper, we have made a proteomics-based review on the role of histone modifications involved in gastrointestinal cancers (GCs) tumorigenesis processes. These alterations function not only as diagnostic or prognostic biomarkers for GCs, but a deeper comprehension of the epigenetic regulation of GCs could facilitate the treatment of this prevalent malignancy through the creation of more effective targeted therapies. [ABSTRACT FROM AUTHOR]

The present perspective article proposes that cachexia, muscle wasting in cancer, is mediated by dysregulated phosphate metabolism and phosphate toxicity that can damage tissues in most major organ systems. A diet high in phosphorus fed to mice deficient in klotho, a cofactor that regulates phosphate metabolism, accelerates aging, sarcopenia, general organ atrophy, kyphosis, and osteoporosis. Similar effects are seen in phenotypes of mutant p53 mice that overexpress the p53 tumor suppressor gene. Although mutant p53 mice do not develop tumors compared to wild-type mice, mutant p53 mice have shorter mean lifespans. Furthermore, tumorigenesis is associated with the sequestration of excessive inorganic phosphate, and dangerous levels of phosphate are released into circulation during tumor lysis syndrome. In total, this evidence implies that tumorigenesis may be a compensatory mechanism that provides protective effects against systemic exposure to dysregulated phosphate metabolism and phosphate toxicity related to cachexia in cancer. Moreover, the hypothetical protection against phosphate toxicity afforded by tumorigenesis also provides an alternate explanation for putative tumor evasion of the immune system. Insights proposed in this perspective paper provide new directions for further research, with potential to develop novel interventions and clinical applications that modify dietary phosphate intake to reduce cachexia in cancer patients. [ABSTRACT FROM AUTHOR]

To explain the sources of additional cell masses in the evolution of multicellular organisms, the theory of carcino-evo-devo, or evolution by tumor neofunctionalization, has been developed. The important demand for a new theory in experimental science is the capability to formulate non-trivial predictions which can be experimentally confirmed. Several non-trivial predictions were formulated using carcino-evo-devo theory, four of which are discussed in the present paper: (1) The number of cellular oncogenes should correspond to the number of cell types in the organism. The evolution of oncogenes, tumor suppressor and differentiation gene classes should proceed concurrently. (2) Evolutionarily new and evolving genes should be specifically expressed in tumors (TSEEN genes). (3) Human orthologs of fish TSEEN genes should acquire progressive functions connected with new cell types, tissues and organs. (4) Selection of tumors for new functions in the organism is possible. Evolutionarily novel organs should recapitulate tumor features in their development. As shown in this paper, these predictions have been confirmed by the laboratory of the author. Thus, we have shown that carcino-evo-devo theory has predictive power, fulfilling a fundamental requirement for a new theory. [ABSTRACT FROM AUTHOR]

Background: Neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) are rare tumoral suppressor syndromes, triggered by an abnormal mutation in a tumour suppressor gene (TSG) (1). Each of these syndromes represents an orphan disease (by itself), but the tumours encountered in these patients are the most frequent lesions of the nervous system. Between the two of these diseases, NF1 presents a greater risk of malignancy, hence the importance of an accurate diagnosis and distinction between the two pathological entities. The purpose of this paper is to describe our department's practice protocol with neurofibromatosis and review the current literature regarding clinical diagnosis and management of these complex diseases. Methods: Our paper is a retrospective study that comprehends 25 patients with neurofibromatosis treated in our clinic between 2011 and 2018. Results: Our study included 16 female patients (64%) and 9 male patients (36%). The mean age at presentation was 48,7 (range 14-72 years). There were 7 cases (28%) of NF1 and 18 cases (72%) of NF2. Seven cases (28%) had a positive family history and 18 patients did not (72%). The most common symptoms at presentation were hearing loss, vertigo, and headache. Conclusions: Neurofibromatosis is a very complex disease in which the tumours may have an unforeseeable growth pattern. New tumours can grow over the years and the symptoms are unpredictable. Surgical treatment is best to be reserved for symptomatic tumours. Non-surgical procedures are also an important step of the treatment, but further studies are required to decide their effectiveness. [ABSTRACT FROM AUTHOR]

Background: Genetic suppression occurs when the deleterious effects of a primary "query" mutation, such as a disease-causing mutation, are rescued by a suppressor mutation elsewhere in the genome. Methods: To capture existing knowledge on suppression relationships between human genes, we examined 2,400 published papers for potential interactions identified through either genetic modification of cultured human cells or through association studies in patients. Results: The resulting network encompassed 476 unique suppression interactions covering a wide spectrum of diseases and biological functions. The interactions frequently linked genes that operate in the same biological process. Suppressors were strongly enriched for genes with a role in stress response or signaling, suggesting that deleterious mutations can often be buffered by modulating signaling cascades or immune responses. Suppressor mutations tended to be deleterious when they occurred in absence of the query mutation, in apparent contrast with their protective role in the presence of the query. We formulated and quantified mechanisms of genetic suppression that could explain 71% of interactions and provided mechanistic insight into disease pathology. Finally, we used these observations to predict suppressor genes in the human genome. Conclusions: The global suppression network allowed us to define principles of genetic suppression that were conserved across diseases, model systems, and species. The emerging frequency of suppression interactions among human genes and range of underlying mechanisms, together with the prevalence of suppression in model organisms, suggest that compensatory mutations may exist for most genetic diseases. [ABSTRACT FROM AUTHOR]

The article titled "[Retracted] miR-218 functions as a tumor suppressor gene in cervical cancer" has been retracted from the journal Molecular Medicine Reports due to concerns about the validity of the data presented. A reader brought to the editor's attention that there were overlapping sections in the data panels, indicating that the results may not have been derived from separate experiments as intended. The authors were asked for an explanation but did not respond. The editor has retracted the paper due to a lack of confidence in the presented data. [Extracted from the article]

Hematological neoplasias, which include cancers of the blood and lymphoid tissues, are common worldwide and have been increasing in incidence. However, the death rate for these cancers has been declining due to advancements in prevention, early detection, and treatment. Understanding the molecular mechanisms involved in hematological neoplasias is crucial for developing targets for prevention, treatment, and biomarkers to improve clinical practice. This special issue focuses on the discovery of novel biomarkers and molecular drug targets in hematological malignancies, with papers discussing various topics such as extracellular vesicles as diagnostic biomarkers, the role of NRF2 in prognosis, and the potential of RNA-binding proteins as targets. The issue also explores new therapeutic strategies and options for patients who do not respond to current treatments. Overall, these advancements contribute to improving approaches to hematological neoplasias. [Extracted from the article]

Aberrant expression of miR-145-5p has been observed in prostate cancer where is has been suggested to play a tumor suppressor role. In other cancers, miR-145-5p acts as an inhibitor of epithelial-to-mesenchymal transition (EMT), a key molecular process for tumor progression. However, the interaction between miR-145-5p and EMT remains to be elucidated in prostate cancer. In this paper the link between miR-145-5p and EMT in prostate cancer was investigated using a combination of in silico and in vitro analyses. miR-145-5p expression was significantly lower in prostate cancer cell lines compared to normal prostate cells. Bioinformatic analysis of The Cancer Genome Atlas prostate adenocarcinoma (TCGA PRAD) data showed significant downregulation of miR-145-5p in prostate cancer, correlating with disease progression. Functional enrichment analysis significantly associated miR-145-5p and its target genes with EMT. MYO6, an EMT-associated gene, was identified and validated as a novel target of miR-145-5p in prostate cancer cells. In vitro manipulation of miR-145-5p levels significantly altered cell proliferation, clonogenicity, migration and expression of EMT-associated markers. Additional TCGA PRAD analysis suggested miR-145-5p tumor expression may be useful predictor of disease recurrence. In summary, this is the first study to report that miR-145-5p may inhibit EMT by targeting MYO6 in prostate cancer cells. The findings suggest miR-145-5p could be a useful diagnostic and prognostic biomarker for prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Phosphatase and tensin homologue (PTEN) is a cancer suppressor gene. Constitutional mutations affecting this gene are associated with several conditions, collectively termed PTEN hamartoma tumour syndromes (PHTS). In addition to hamartomas, PTEN aberrations have been associated with a range of non-tumoural phenotypes such as macrocephaly, and research indicates possibly increased rates of developmental delay and autism spectrum disorder (ASD) for people with germline mutations affecting PTEN. Method: A systematic review of literature reporting behavioural and psychological variables for people with constitutional PTEN mutations/PHTS was conducted using four databases. Following in-depth screening, 25 articles met the inclusion criteria and were used in the review. Fourteen papers reported the proportion of people with PTEN mutations/PTHS meeting criteria for or having characteristics of ASD and were thus used in a pooled prevalence meta-analysis. Results: Meta-analysis using a random effects model estimated pooled prevalence of ASD characteristics at 25% (95% CI 16–33%), although this should be interpreted cautiously due to possible biases in existing literature. Intellectual disability and developmental delay (global, motor and speech and language) were also reported frequently. Emotional difficulties and impaired cognitive functioning in specific domains were noted but assessed/reported less frequently. Methods of assessment of psychological/behavioural factors varied widely (with retrospective examination of medical records common). Conclusions: Existing research suggests approximately 25% of people with constitutional PTEN mutations may meet criteria for or have characteristics of ASD. Studies have also begun to establish a range of possible cognitive impairments in affected individuals, especially when ASD is also reported. However, further large-scale studies are needed to elucidate psychological/behavioural corollaries of this mutation, and how they may relate to physiological/physical characteristics. [ABSTRACT FROM AUTHOR]

Three novel Zn(II) complexes [ZnCl2(H2LtBu)] , [ZnCl2(Me2LtBu)] and [Zn2Cl4(H2LCatBiPyPh)2] (where H2LtBu is 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine, Me2LtBu is 2,6-bis(5-tert-butyl-1-methyl-1H-pyrazol-3-yl)pyridine and H2LCatBiPyrPh is 1,2-bis((5-phenyl-1H-pyrazol-3-yl)methoxy)benzene) were synthesized and characterized using various spectroscopic techniques, including UV-vis, IR, 1D (1H and 13C) and 2D (1H–1H COSY) NMR. The structures of complexes [ZnCl2(H2LtBu)] and [Zn2Cl4(H2LCatBiPyPh)2] were elucidated through X-ray crystallography. The interactions of the complexes with CT-DNA and human serum albumin (HSA) were investigated using UV-vis spectroscopy and fluorescence emission titration. All examined complexes exhibited quenching constant, Ksv, values in the order of 104 with CT-DNA. Constant values followed the trend [ZnCl2(Me2LtBu)] < [Zn2Cl4(H2LCatBiPyPh)2] < [ZnCl2(H2LtBu)]. The results indicated a moderate interaction between the complexes and HSA. In terms of cytotoxic activity, the zinc(II) complexes significantly decreased the viability of colon (HCT-116) and pancreatic (MIA PaCa-2) cancer cell lines, where the effect on pancreatic cells after 72 h is especially emphasized. The most pronounced occurrence of apoptosis, as the dominant type of complex-induced cell death, was associated with complex [ZnCl2(H2LtBu)] , while necrosis was observed at lower percentages in all investigated treatments. All complexes demonstrated downregulation of the tumor suppressor gene TP53 (homo sapiens tumor protein p53). Treatment with [ZnCl2(H2LtBu)] resulted in downregulation of TP53, CASP3 (Caspase 3) and IGF1R (insulin-like growth factor 1), potentially impairing the effective apoptotic process and reducing cell proliferation. [ABSTRACT FROM AUTHOR]

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and nonprogrammed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by uncontrolled proliferation and impaired differentiation of myeloid cells in the bone marrow. The tumor suppressor gene TP53 plays a crucial role in maintaining genomic integrity and preventing the development of cancer. TP53 mutations are frequently observed in AML (∼10% of patients) and are associated with aggressive disease behavior, resistance to therapy, and poor prognosis. Summary: Recent changes in classification of TP53-mutated myelodysplastic syndrome (MDS) have occurred related to the allelic status of TP53 and more importantly to harmonize MDS/AML patients as a homogeneous hematological malignancy. Current treatment regimens involve hypomethylating agents +/− venetoclax or intensive chemotherapy although unfortunately independent of treatment regimen the overall survival (OS) of this patient cohort is around 6 months with poor long-term outcomes after allogeneic stem-cell transplantation. Recent developments geared toward the treatment of TP53-mutated MDS/AML have focused on immunotherapies. Key Messages: Notably, there is optimism surrounding these new therapies that could provide breakthroughs with improving outcomes either as monotherapy or combined with established nonimmune therapies. This paper aims to provide an overview of TP53-mutated MDS/AML, including the underlying mechanisms, clinical implications, and emerging therapeutic strategies targeting this hematologic malignancy. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common malignancy in the world and one of the leading causes of cancer death, which is a heterogeneous disease involving genetic and environmental factors. Breast cancer stem cells (BCSCs) are the main players in the aggressiveness of different tumors, at the same time, these cells are the main challenge for cancer treatment. There are multiple treatment options for breast cancer (BC) patients and the lack of understanding of prognostic and predictive biomarkers for breast cancer is a potential research direction for us to develop better treatments in the future. In this paper, we conducted a correlation analysis between SIK2 and clinical traits by searching numerous BRCA datasets in the GEO database. The model was constructed and validated by incorporating tumor samples from the TCGA‐BRCA cohort. Surprisingly, we found differential expression of SIK2 gene in individual tumor samples from the UCSC database. Subsequently, we found significantly high expression of SIK2 in epithelial cells by comparing the differential expression of SIK2 in different cell subpopulations and performed subsequent immune infiltration and pathway correlation analysis. Differential genes in SIK2+ epithelial cells, which may be potential therapeutic targets for breast cancer. In conclusion, our results suggest that SIK2 may be a potential prognostic and predictive biomarker that could serve as an oncogenic messenger for breast cancer. This discovery of SIK2 may provide more valuable references for potential therapeutic tools for breast cancer. [ABSTRACT FROM AUTHOR]

C-terminal binding protein 1 (CtBP1) is a critical transcriptional corepressor of many tumor suppressor genes and plays diverse roles in the progression of cancers. The transcriptional repression function of CtBP1 is mediated by recruiting histone-modifying enzymes, such as histone deacetylases and histone methyltransferases, to target genes by binding with DNA-interacting factors. Several post-translational modifications of CtBP1 have been identified, including ubiquitination, phosphorylation, and SUMOylation. This paper reports that CtBP1 is conjugated by ISG15. Endogenous CtBP1 was modified by ISG15 after interferon-α treatment in HeLa cells. The ISGylation process of CtBP1 was regulated by deISGylation enzyme USP18 and ISG15 E3 ligase EFP. Interestingly, CtBP1 ISGylation affected the binding affinity between CtBP1 and some components of CtBP1-associated transcriptional complexes. HDAC1 and LSD1 bound more efficiently to ISG15-conjugated CtBP1 than non-conjugated CtBP1. On the other hand, binding between CtBP1 and HDAC4 was unaffected by ISG15 modification. Furthermore, ISG15 modification enhanced the transcriptional repression activity of CtBP1 on several target genes related to EMT and apoptosis. These findings suggest that the ISG15 modification of CtBP1 modulates the function and activity of CtBP1 and that CtBP1 ISGylation may provide a new insight for CtBP1-mediated cancers. [ABSTRACT FROM AUTHOR]

Most biosynthetic gene clusters (BGCs) of Actinobacteria are either silent or expressed less than the detectable level. The non-genetic approaches including biological interactions, chemical agents, and physical stresses that can be used to awaken silenced pathways are compared in this paper. These non-genetic induction strategies often need screening approaches, including one strain many compounds (OSMAC), reporter-guided mutant selection, and high throughput elicitor screening (HiTES) have been developed. Different types of genetic manipulations applied in the induction of cryptic BGCs of Actinobacteria can be categorized as genome-wide pleiotropic and targeted approaches like manipulation of global regulatory systems, modulation of regulatory genes, ribosome and engineering of RNA polymerase or phosphopantheteine transferases. Targeted approaches including genome editing by CRISPR, mutation in transcription factors and modification of BGCs promoters, inactivation of the highly expressed biosynthetic pathways, deleting the suppressors or awakening the activators, heterologous expression, or refactoring of gene clusters can be applied for activation of pathways which are predicted to synthesize new bioactive structures in genome mining studies of Acinobacteria. In this review, the challenges and advantages of employing these approaches in induction of Actinobacteria BGCs are discussed. Further, novel natural products needed as drug for pharmaceutical industry or as biofertilizers in agricultural industry can be discovered even from known species of Actinobactera by the innovative approaches of metabolite biosynthesis elicitation. [ABSTRACT FROM AUTHOR]

In this paper, we use pattern analysis in genetic networks to identify differentially expressed genes in primary breast cancer tumors and their first metastasis in lymph nodes, using human biopsies from the GEO and GDCDP databases. By applying Information-Theory-based algorithms to process gene expression profile matrices, we obtained the genetic networks of the following tissues: (1) breast cancer-free, (2) primary breast cancer tumors, and (3) first metastasis of breast cancer in lymph nodes. Topological analysis of the genetic networks delves for identifying patterns of pairs of genes with higher mutual information than a threshold; then, among these genes, the ones with highest degree are elected. We propose the plausible hypothesis that the elected genes, having principal roles in each network, could be relevant as biomarkers regarding the genetic information. A subsequent gene ontology-based analysis of the molecular and functional characteristics of these genes reveals specific signaling pathways signatures in cancer-free tissue and in the tumor microenvironment associated with primary and metastatic requirements. Furthermore, a state-of-the-art review of the functional roles of genes reveals tumor suppressor genes in cancer-free tissue and proliferation- and migration-associated genes in cancer. • Genetic network (GN) patter analysis for identifying hub genes in breast cancer data. • Entropy and mutual information used for identifying main genes in breast cancer GN. • GN genes with higher mutual information and degree would emerge as cancer biomarkers. • Main genes segregate in genetic signature associated with specific signaling pathways. [ABSTRACT FROM AUTHOR]

CXCL14 is one of the most evolutionarily conserved members of the chemokine family and is constitutionally expressed in multiple organs, suggesting that it is involved in the homeostasis maintenance of the system. CXCL14 is highly expressed in colon epithelial cells and shows obvious gene silencing in clinical colon cancer samples, suggesting that its silencing is related to the immune escape of cancer cells. In this paper, we analyzed the expression profiles of multiple human clinical colon cancer datasets and mouse colon cancer models to reveal the variation trend of CXCL14 expression during colitis, colon polyps, primary colon cancer, and liver metastases. The relationship between CXCL14 gene silencing and promoter hypermethylation was revealed through the colorectal carcinoma methylation database. The results suggest that CXCL14 is a tumor suppressor gene in colorectal carcinoma which is activated first and then silenced during the process of tumor occurrence and deterioration. Promoter hypermethylation is the main cause of CXCL14 silencing. The methylation level of CXCL14 is correlated with the anatomic site of tumor occurrence, positively correlated with patient age, and associated with prognosis. Reversing the hypermethylation of CXCL14 may be an epigenetic therapy for colon cancer. [ABSTRACT FROM AUTHOR]

TAB182 participates in DNA damage repair and radio-/chemosensitivity regulation in various tumors, but its role in tumorigenesis and therapeutic resistance in breast cancer remains unclear. In the current paper, we observed that triple-negative Breast Cancer (TNBC), a highly aggressive type of breast cancer, exhibits a lower expression of TAB182. TAB182 knockdown stimulates the proliferation, migration, and invasion of TNBC cells. Our study first obtained RNA-seq data to explore the cellular functions mediated by TAB182 at the genome level in TNBC cells. A transcriptome analysis and in vitro experiments enabled us to identify that TAB182 downregulation drives the enhanced properties of cancer stem-like cells (CSCs) in TNBC cells. Furthermore, TAB182 deletion contributes to the resistance of cells to olaparib or cisplatin, which can be rescued by silencing GLI2, a gene downstream of cancer stemness-related signaling pathways. Our results reveal a novel function of TAB182 as a potential negative regulator of cancer stem-like properties and drug sensitivity in TNBC cells, suggesting that TAB182 may be a tumor suppressor gene and is associated with increased therapeutic benefits for TNBC patients. [ABSTRACT FROM AUTHOR]

The Schlafen5(SLFN5)gene belongs to the third group of the Schlafen protein family. As a tumor suppressor gene, SLFN5 plays a pivotal role in inhibiting tumor growth, orchestrating cell cycle regulation, and modulating the extent of cancer cell infiltration and metastasis in various malignancies. However, the high expression of SLFN 5 in some tumors was positively correlated with lymph node metastasis, tumor stage, and tumor grade. This article endeavors to elucidate the reciprocal relationship between the SLFN5 gene and malignant tumors, thereby enhancing our comprehension of the intricate mechanisms underlying the SLFN5 gene and its implications for the progression, invasive potential, and metastatic behavior of malignant tumors. At the same time, this paper summarizes the basis of SLFN 5 as a new biomarker of tumor diagnosis and prognosis, and provides new ideas for the target treatment of tumor. [ABSTRACT FROM AUTHOR]

The neurofibromatosis-1 gene (NF1) was initially characterized because its germline mutation is responsible for an inherited syndromic disease predisposing tumor development, in particular neurofibromas but also various malignancies. Recently, large-scale tumor sequencing efforts have demonstrated NF1 as one of the most frequently mutated genes in human cancer, being mutated in approximately 5–10% of all tumors, especially in malignant peripheral nerve sheath tumors and different skin tumors. NF1 acts as a tumor suppressor gene that encodes neurofibromin, a large protein that controls neoplastic transformation through several molecular mechanisms. On the other hand, neurofibromin loss due to NF1 biallelic inactivation induces tumorigenic hyperactivation of Ras and mTOR signaling pathways. Moreover, neurofibromin controls actin cytoskeleton structure and the metaphase–anaphase transition. Consequently, neurofibromin deficiency favors cell mobility and proliferation as well as chromosomal instability and aneuploidy, respectively. Growing evidence supports the role of oxidative stress in NF1-related tumorigenesis. Neurofibromin loss induces oxidative stress both directly and through Ras and mTOR signaling activation. Notably, innovative therapeutic approaches explore drug combinations that further increase reactive oxygen species to boost the oxidative unbalance of NF1-altered cancer cells. In our paper, we review NF1-related tumors and their pathogenesis, highlighting the twofold contribution of oxidative stress, both tumorigenic and therapeutic. [ABSTRACT FROM AUTHOR]

Introduction: Colon cancer is a complex disease that involves intricate interactions between cancer cells and theimmune microenvironment. MicroRNAs (miRNAs) have recently emerged as critical regulators of gene expression in cancer, including colon cancer. There is increasing evidence suggesting that miRNA dysregulation plays a crucial role in modulating the immune microenvironment of intestinal cancer. In particular, miRNAs regulate immune cell activation, differentiation, and function, as well as cytokine and chemokine production in intestinal cancer. It is urgent to fully investigate the potential role of intestinal cancer-related miRNAs in shaping the immune microenvironment. Methods: Therefore, this paper aims to identify miRNAs that are potentially associated with colon cancer and regulate a large number of genes related to immune function. We explored the role of these genes in colon cancer patient prognosis, immune infiltration, and tumor purity based on data of 174 colon cancer patients though convolutional neural network, survival analysis and multiple analysis tools. Results: Our findings suggest that miRNA regulated genes play important roles in CD4 memory resting cells, macrophages.M2, and Mast cell activated cells, and they are concentrated in the cytokinecytokine receptor interaction pathway. Discussion: Our study enhances our understanding of the underlying mechanisms of intestinal cancer and provides new insights into the development of effective therapies. Additionally, identification of miRNA biomarkers could aid in diagnosis and prognosis, as well as guide personalized treatment strategies for patients with intestinal cancer. [ABSTRACT FROM AUTHOR]

Lists papers to be published in forthcoming issues of the "British Journal of Haematology." Thromboembolic risks for women; Link between tolerance associated with cord blood transplantation and the state of host dendritic cells; Low expression of the putative tumor suppressor gene gravin in chronic myeloid leukemia.

Oral squamous cell carcinoma (OSCC) is the most common malignant cancer of the head and neck, with high morbidity and mortality, ranking as the sixth most common cancer in the world. The treatment of OSCC is mainly radiotherapy, chemotherapy and surgery, however, the prognosis of patients is still poor and the recurrence rate is high. This paper reviews the range of effects of natural medicinal plant active ingredients (NMPAIs) on OSCC cancer, including the types of NMPAIs, anti-cancer mechanisms, involved signaling pathways, and clinical trials. The NMPAIs include terpenoids, phenols, flavonoids, glycosides, alkaloids, coumarins, and volatile oils. These active ingredients inhibit proliferation, induce apoptosis and autophagy, inhibit migration and invasion of OSCC cells, and regulate cancer immunity to exert anti-cancer effects. The mechanism involves signaling pathways such as mitogen-activated protein kinase, phosphatidylinositol 3 kinase/protein kinase B, nuclear factor kappa B, miR-22/WNT1/β-catenin and Nrf2/Keap1. Clinically, NMPAIs can inhibit the growth of OSCC, and the combined drug is more effective. Natural medicinal plants are promising candidates for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Background: Speckle Type POZ Protein (SPOP), despite its tumor type-dependent role in tumorigenesis, primarily as a tumor suppressor gene is associated with a variety of different cancers. However, its function in pancreatic cancer remains uncertain. Methods: SPOP expression and the association between its expression and patient prognosis and immune function were evaluated using The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), The Tumor Immune Estimation Resource 2.0 (TIMER2.0) database, cBioportal, and various bioinformatic databases. Enrichment analysis of SPOP and the association between SPOP expression with clinical stage and grade were analyzed using the R software package. Then immunohistochemistry (IHC) was used to estimate the correlation between SPOP and tumor-infiltrating lymphocytes (TILs) in patients with pancreatic cancer. Results: As part of our study, we assessed that SPOP was anomalously expressed in kinds of cancers, associated with clinical stage and outcomes. Meanwhile, SPOP also played a crucial role in the tumor microenvironment (TME). The expression level of SPOP was significantly correlated to tumor-infiltrating immune cells (TICs) in pancreatic cancer. Conclusions: Our study uncovered the potential corrections in SPOP with TICs, suggesting that SPOP may act as a biomarker for immunotherapy in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent cancer in the world. Currently, the main treatments for breast cancer are radiotherapy, chemotherapy, targeted therapy and surgery. The treatment measures for breast cancer depend on the molecular subtype. Thus, the exploration of the underlying molecular mechanisms and therapeutic targets for breast cancer remains a hotspot in research. In breast cancer, a high level of expression of DNMTs is highly correlated with poor prognosis, that is, the abnormal methylation of tumor suppressor genes usually promotes tumorigenesis and progression. MiRNAs, as non-coding RNAs, have been identified to play key roles in breast cancer. The aberrant methylation of miRNAs could lead to drug resistance during the aforementioned treatment. Therefore, the regulation of miRNA methylation might serve as a therapeutic target in breast cancer. In this paper, we reviewed studies on the regulatory mechanisms of miRNA and DNA methylation in breast cancer from the last decade, focusing on the promoter region of tumor suppressor miRNAs methylated by DNMTs and the highly expressed oncogenic miRNAs inhibited by DNMTs or activating TETs. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis. [ABSTRACT FROM AUTHOR]

This document is a special issue of the International Journal of Molecular Sciences focusing on new advances in cancer genetics. The papers collected in this issue discuss various mechanisms of tumorigenesis, the challenges in exploring them, and the need for multiple perspectives. The studies highlight the role of miRNAs in tumor formation, pathways involved in altering tumor suppressor genes, and the potential of new methods like cfDNA and ctDNA analysis for patient monitoring and management. However, these methods require validation and refinement, and it is important to recognize the complexity of tumor progression and the need for alternative disease monitoring tools. The document emphasizes the fragmentation of knowledge in cancer research and the challenge of integrating this knowledge into effective clinical management models. [Extracted from the article]

Simple Summary: A low level of oxygen (hypoxia) is a common feature of many solid tumours. Tumour hypoxia is a contributing factor to prostate cancer progression and is known to cause the abnormal expression of many important genes, including microRNAs. In this study, we investigate the link between hypoxia and microRNA-21 (miR-21) in prostate cancer cells. We use in vitro and in vivo models to show that miR-21 expression is induced by hypoxia in prostate cells, which we propose explains why miR-21 up-regulation is a feature of prostate tumours. We demonstrate that miR-21 up-regulation can alter the behaviour of normal prostate cells and we further show for the first time in prostate cancer that it down-regulates RHOB, a tumour suppressor gene. We finish by presenting data to suggest miR-21 has considerable potential as a biomarker of hypoxia that can aid in the diagnosis and prognosis of prostate cancer. Tumour hypoxia is a well-established contributor to prostate cancer progression and is also known to alter the expression of several microRNAs. The over-expression of microRNA-21 (miR-21) has been consistently linked with many cancers, but its role in the hypoxic prostate tumour environment has not been well studied. In this paper, the link between hypoxia and miR-21 in prostate cancer is investigated. A bioinformatic analysis of The Cancer Genome Atlas (TCGA) prostate biopsy datasets shows the up-regulation of miR-21 is significantly associated with prostate cancer and clinical markers of disease progression. This up-regulation of miR-21 expression was shown to be caused by hypoxia in the LNCaP prostate cancer cell line in vitro and in an in vivo prostate tumour xenograft model. A functional enrichment analysis also revealed a significant association of miR-21 and its target genes with processes related to cellular hypoxia. The over-expression of miR-21 increased the migration and colony-forming ability of RWPE-1 normal prostate cells. In vitro and in silico analyses demonstrated that miR-21 down-regulates the tumour suppressor gene Ras Homolog Family Member B (RHOB) in prostate cancer. Further a TCGA analysis illustrated that miR-21 can distinguish between different patient outcomes following therapy. This study presents evidence that hypoxia is a key contributor to the over-expression of miR-21 in prostate tumours, which can subsequently promote prostate cancer progression by suppressing RHOB expression. We propose that miR-21 has good potential as a clinically useful diagnostic and prognostic biomarker of hypoxia and prostate cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in molecular genetics have radically changed all aspects of cancer prevention, screening and treatment and, today, women who are suspected of being at risk of hereditary cancer should always undergo genetic counselling. Furthermore, today there is growing attention on the tumor suppressor genes BRCA 1 and BRCA2. In addition, there is growing attention on women who carry mutations of the tumor suppressor genes BRCA 1 and BRCA2 and undergo a prophylactic risk-reducing salpingo-oophorectomy. This paper explores the pathobiology of BRCA1\2 cancer genes in a translational perspective, focusing on molecular aspects of hormonal therapy in early menopausal women as well as on the latest evidence-based guidelines for clinicians. Physicians should counsel motivated patients who ask for relief from early menopausal symptoms about the risks and benefits of hormonal therapy, as well as tailoring and appropriate treatment for selected patients. All cancers develop as a result of mutations in genes. DNA damage induces genomic instability and subsequently increases susceptibility to tumorigenesis. Women who carry mutations of BRCA 1 and BRCA2 genes have an augmented risk of breast and ovarian cancer and a markedly augmented probability of dying because of cancer compared to the general population. As a result, international guidelines recommend that all BRCA1\2 mutation carriers be offered risk-reducing bilateral salpingo-oophorectomy at an early age to reduce the risk of cancer and decrease the mortality rate of this high-risk population. NCCN guidelines recommend risk-reducing bilateral salpingo-oophorectomy in pre-menopausal women, between 35–40 years in BRCA1 mutation carriers and between 40–45 years in BRCA2 mutation carriers. Unfortunately, the well-documented reduction of cancer risk is counterbalanced by early sterility and premature ovarian failure with an early onset of secondary menopausal syndromes such as neuromotor, cardiovascular, cognitive and urogenital deficiency. Hormonal replacement therapy significantly compensates for hormonal deprivation and counteracts menopausal syndrome morbidity and mortality; however, some data suggest a possible correlation between hormonal medications and cancer risk, especially in BRCA1\2 carriers who undergo long-term regimens. Conversely, short-term treatment before the age of natural menopause does not appear to increase the cancer risk in BRCA1 mutation carriers without a personal history of breast cancer after prophylactic surgery. Few data are available on BRCA2 mutation carriers and more well-designed studies are needed. In conclusion, clinicians should propose short-term hormone replacement therapy to BRCA 1 carriers to counteract hormonal deprivation; personalized counselling should be offered to BRCA2 mutation carriers for a balance between the risks and benefits of the treatment. [ABSTRACT FROM AUTHOR]

As the third most common cancer and the second leading cause of cancer death worldwide, colorectal cancer (CRC) poses a serious threat to people's health. In recent years, circRNA has been widely reported as a new biomarker in CRC, but a comprehensive summary and analysis is lacking. This study aims to evaluate the diagnostic, therapeutic and prognostic significance of circRNAs in CRC by systematically analysing their expression patterns, biological functions and clinical significance in CRC. The literature on circRNA in CRCwas searched in the PubMed database and included for analysis after screening according to strict inclusion and exclusion criteria. The UALCAN online tool was used to obtain host gene expression data. The miRTargetLink 2.0 was used to predict target genes for miRNAs action in CRC patients. Cytoscape was used to construct circRNA-miRNA-mRNA interaction networks. From the 236 included papers, we identified 217 circRNAs and their associated 108 host genes and 145miRNAs.Among the 145miRNAs, 27 miRNAs had no corresponding target genes. After prediction of target genes and differential analysis, a total of 25 target genes were obtained and a circRNA-miRNA-mRNA interaction network was constructed. Among the 217 circRNAs, 74 were associated with diagnosis, 160 with treatment and 51 with prognosis. And 154 of themfunction as oncogenes while 58 as tumour suppressor genes. In addition, these circRNAs include 32 exosomal circRNAs, which have unique advantages as biomarkers. In total, we summarize and analyze the expression patterns, biological functions and clinical significance of circRNAs in CRC. In addition, we constructed some new circRNA-miRNA-mRNA regulatory axes based on themiRNAs sponged by circRNAs. [ABSTRACT FROM AUTHOR]

The role of long non-coding RNA (lncRNA) in human tumors has gradually received increasing attention in recent years. Particularly, the different functions of lncRNAs in different subcellular localizations have been widely investigated. The upregulation of lncRNA small nucleolar RNA host gene 17 (SNHG17) has been observed in various human tumors. Growing evidence has proved that SNHG17 plays a tumor-promoting role in tumorigenesis and development. This paper describes the molecular mechanisms by which SNHG17 contributes to tumor formation and development. The different functions of SNHG17 in various subcellular localizations are also emphasized: its function in the cytoplasm as a competing endogenous RNA (ceRNA), its action in the nucleus as a transcriptional coactivator, and its function through the polycomb repressive complex 2 (PRC2)-dependent epigenetic modifications that regulate transcriptional processes. Finally, the correlation between SNHG17 and human tumors is summarized. Its potential as a novel prognostic and diagnostic biomarker for cancer is explored especially. [ABSTRACT FROM AUTHOR]