Mutation Research

PARP inhibitors inflict severe toxicity to homologous recombination (HR) repair deficient cells because DNA damages induced by PARP inhibition result in lethal DNA double strand breaks in the absence of HR repair during DNA replication. PARP inhibitors are the first clinically approved drugs designed for synthetic lethality. The synthetic lethal interaction of PARP inhibitors is not limited to HR repair deficient cells. We investigated radiosensitive mutants isolated from Chinese hamster lung origin V79 cells to identify novel synthetic lethal targets in the context of PARP inhibition...

Mutagenesis can be thought of as random, in the sense that the occurrence of each mutational event cannot be predicted with precision in space or time. However, when sufficiently large numbers of mutations are analyzed, recurrent patterns of base changes called mutational signatures can be identified. To date, some 60 single base substitution or SBS signatures have been derived from analysis of cancer genomics data. We recently reported that the ubiquitous signature SBS5 matches the pattern of single nucleotide polymorphisms (SNPs) in humans and has analogs in many species...

OBJECTIVE: Examine whether DNA repair capacity (DRC) levels are associated with body mass index (BMI) in adult women. DESIGN AND PARTICIPANTS: A nested study composed of 539 women without breast cancer (BC) from a case-control BC study in addition to 104 that were recruited later for a total of 643. MEASUREMENTS: DRC levels were measured in lymphocytes using a host-cell reactivation assay with a luciferase reporter gene damaged by UVC. This assay measures the efficiency of nucleotide excision repair (NER)...

Barth syndrome is a rare disease affecting mitochondria structure and function in males. In our previous study, we have shown a new mutation (c.83T>A, p.Val28Glu) in the TAZ gene in two affected patients with congenital cardiomyopathy. Furthermore, women in this family had no mutations in their blood cells, whereas they only had mutations in the oral epithelial cells. The objective of the project was to evaluate the effect of intertissue mosaicisms on the Barth syndrome phenotypes, searching for another disease-related loci on chromosome X and finally to assess the consequences of the mutation...

Searching for differential genes in lung adenocarcinoma (LUAD) is vital for research. Hyaluronan mediated motility receptor (HMMR) promotes malignant progression of cancer patients. However, the molecular regulators of HMMR-mediated LUAD onset are unknown. This work aimed to study the relevance of HMMR to proliferation, migration and invasion of LUAD cells. Let-7c-5p and HMMR levels in LUAD cells and HLF-a cells were assessed, and their correlation was also detected. Their interaction was determined by dual-luciferase experiments and qRT-PCR...

BACKGROUND: Increasing evidence shows that Transmembrane 4 L6 family member 1(TM4SF1) exerts a critical role in mediating the progression of various tumors. Nevertheless, the exact mechanism of TM4SF1 in gastric cancer (GC) remains unclear. METHODS: Bioinformatics analysis was utilized to analyze TM4SF1 expression in GC tissues. Also, MiRWalk and starBase databases were used to predict the upstream microRNAs which could regulate TM4SF1 expression. Gene set enrichment analysis (GSEA) for TM4SF1 was conducted to screen the potentially involved pathways...

PURPOSE: The study objects were to explore the correlation between the biological role of clock genes and clinical indicators in patients with osteosarcoma (OS). METHODS: We acquired the clinical information and RNA sequencing data of OS samples from the TARGET database. The protein-protein interaction (PPI) network and expression correlation analysis of clock genes were performed. Then, the functional enrichment analysis of clock genes was analyzed. The survival analysis of clock genes in patients of OS was carried out by univariate cox regression, Kaplan-Meier (KM) curve and multivariate cox regression methods...

PTEN is a tumor suppressor protein frequently altered in various cancers. PTEN-null cells have a characteristic of rapid proliferation with an unstable genome. Replication stress is one of the causes of the accumulation of genomic instability if not sensed by the cellular signaling. Though PTEN-null cells have shown to be impaired in replication progression and stalled fork recovery, the association between the catalytic function of PTEN regulated by posttranslational modulation and cellular response to replication stress has not been studied explicitly...

The high level natural radiation areas (HLNRA) of Kerala coast provide unique opportunity to study the biological effect of chronic low dose ionizing radiation (LDIR) on human population below 100 mSv. The radiation level in this area varies from < 1.0-45 mGy /year due to patchy distribution of monazite in the sand, which contains 232 Th (8-10%), 238 U (0.3%), and their decay products. Telomere length attrition has been correlated to DNA damage due to genotoxic agents. The objective of the present study is to evaluate the effect of natural chronic LDIR exposure on telomere length and transcriptional response of telomere specific and DNA damage repair genes in peripheral blood mononuclear cells (PBMCs) of individuals from normal level natural radiation areas (NLNRA) and HLNRA of Kerala coast, southwest India...

Rheumatoid arthritis (RA), which is driven by persistent activation of the immune system, primarily affects the joints. Several reports have estimated the risk of gonadal disruptions in arthritic patients, with potential attributable risk factors such as treatments with the disease-modifying antirheumatic drugs and the influence of the disease itself. The FDA approved rituximab, a therapy for non-Hodgkin's lymphoma, for management of RA in February 2006. However, the influence of repeated treatment with rituximab on gonadal function in RA has not been reported yet...

BACKGROUND: Lung adenocarcinoma (LUAD) belongs to non-small cell lung cancer. In addition to surgical resection, chemotherapy and radiotherapy cause great side effects and low 5-year survival rates. MiRNAs are closely related to cancer development. This study aimed to analyze the molecular mechanism of miRNA-144-5p targeting CDCA3 to inhibit LUAD proliferation. METHODS: MiRNA and mRNA data were downloaded from TCGA-LUAD dataset for differential expression analysis...

Royal jelly (RJ) is a creamy white-yellow liquid that is secreted by the mandibular and hypopharyngeal glands of bees to nourish the larvae. RJ has gained increasing interest in recent years owing to its antioxidant potential. However, little is known about adequate RJ dosing and its effects on genetic material. Thus, the aim of this study was to evaluate the in vivo effects of RJ on genotoxicity and mutagenicity induced by the alkylating agent methyl methanesulfonate (MMS). In this study, 3-month-old Swiss albino male mice (N = 66) were divided into 11 groups for experimentation...

8-Oxo-7,8-dihydroguanine (8-hydroxyguanine, G°) is a major oxidized base that is considered to play pivotal roles in the pathogenesis of various diseases, including cancer. G° induces G:C → T:A transversions at the damage site and untargeted (action-at-a-distance) mutations of G bases at 5'-GpA sequences. In this study, we examined the distribution of the action-at-a-distance mutations and the effects of the replication origin position relative to G° on the untargeted mutagenesis. The G° base was introduced into two shuttle plasmids, each with the SV40 replication origin at a different position with respect to the supF gene...

In this study, mRNA expression of gastric cancer tissue and clinical data of patients in TCGA-STAD dataset were used, together with the hypoxia-related gene sets in the MsigDB database, to screen hypoxia-related differentially expressed genes (DEGs) in GC. Thereafter, univariate and multivariate Cox regression analyses were carried out on hypoxia-related DEGs. The optimal feature genes related to prognosis were obtained to construct a prognostic risk assessment model. According to the model, the riskScore of GC patients was measured, and GC samples were assigned into high- and low-risk groups in accordance with the median riskScore...

BACKGROUND: Biological mechanism of miR-210-3p in endometrial carcinoma (EC) remains unclear. Here, our purpose is to study effects of miR-210-3p on malignant progression of EC. METHODS: Bioinformatics analysis showed miRNA and mRNA are abnormally expressed in EC tissues. Quantitative real-time fluorescence polymerase chain reaction (qRT-PCR) was utilized to compare miR-210-3p mRNA level in EC cells and tissues. qRT-PCR and western blot were used to measure RUNX1T1 and NCAM1 at mRNA and protein levels, and western blot for p-AKT and AKT proteins related to PI3K/AKT signaling pathway...

BACKGROUND: Lung adenocarcinoma (LUAD) is featured in high morbidity and mortality. Aberrant activation of the histone methyltransferase EZH2 has close association with cancer progression. This research aimed to deeply dive into the role and possible molecular mechanisms of EZH2 and its downstream genes in malignant progression and DNA damage repair of LUAD cells. METHODS: Expression of EZH2 in LUAD cells was analyzed by qRT-PCR, and the effects of EZH2 on proliferation, and apoptosis of LUAD cells were examined by CCK-8, colony formation and flow cytometry assays...

OBJECTIVE: This study attempted to investigate the mechanism of miR-204-5p and its downstream gene in regulating bio-functions of esophageal cancer (EC). METHODS: Bioinformatics analysis was performed to select the mature miRNAs, mRNAs, and clinical data of EC. The miRNA-mRNA regulatory axis was predicted through bioinformatics and used Dual-luciferase analysis to verify the interaction between miR-204-5p and APLN. qRT-PCR was applied to analyze expression of miR-204-5p and APLN mRNA...

Acute kidney injury (AKI) is a common clinical disease that can cause serious harm to the kidneys, but it has no effective treatment till now. The modulation of autophagy pathway regulation is considered a potentially effective therapeutic approach in AKI prevention and treatment. ZKSCAN3 has been shown to be an important transcription factor that negatively regulates autophagy activity in cancer tissues. In order to determine whether autophagy could be activated by knocking out ZKSCAN3 to exert the renal protective effect of autophagy, we constructed AKI models with Zkscan3 knockout (KO) mice and detected renal pathological changes and renal function changes as well as autophagy-related indicators...

No abstract text is available yet for this article.

Lamin proteins which constitute the nuclear lamina in almost all higher eukaryotes, are mainly of two types A & B encoded by LMNA and LMNB1/B2 genes respectively. While lamin A remains the principal product of LMNA gene, variants like lamin C, C2 and A∆10 are also formed as alternate splice products. Role of lamin A in aging has been highlighted in recent times due to its association with progeroid or premature aging syndromes which is classified as a type of laminopathy. Progeria caused by accelerated accumulation of lamin A Δ50 or progerin occurs due to a mutation in this LMNA gene leading to defects in post translational modification of lamin A...