The TopBP1-ATR axis is critical for maintaining genomic stability during DNA replication stress, yet the precise regulation of TopBP1 in replication stress responses remains poorly understood. In this study, we identified PHD and Ring Finger Domains 1 (PHRF1) as an important ATR activator through its interaction with TopBP1. Our analysis revealed a correlation between PHRF1 and genomic stability in cancer patients.
View Article and Find Full Text PDFMost patients with metastatic prostate cancer eventually develop resistance to primary androgen deprivation therapy. To identify predictive biomarker for Abiraterone acetate/prednisone resistance, we screened alternative splice variants between responders and non-responders from the PROMOTE clinical study and pinned down the most significant variant, CENPK-delta8. Through preclinical patient-derived mouse xenograft (PDX) and 3D organoids obtained from responders and non-responders, as well as in vitro models, aberrant CENPK-delta8 expression was determined to link to drug resistance via enhanced migration and proliferation.
View Article and Find Full Text PDFBiomed Pharmacother
December 2023
Lung squamous cell carcinoma (LUSC) is a non-small cell lung cancer with a poor prognosis owing to late diagnosis. New molecular markers are urgently needed to improve the diagnosis and prognosis of LUSC. 7-Methylguanosine (mG) modifications, a tRNA modification, are common in eubacteria, eukaryotes, and a few archaea.
View Article and Find Full Text PDFDNA damage is a double-edged sword in cancer cells. On the one hand, DNA damage exacerbates gene mutation frequency and cancer risk. Mutations in key DNA repair genes, such as breast cancer 1 () and/or breast cancer 2 (), induce genomic instability and promote tumorigenesis.
View Article and Find Full Text PDFIn this study, a novel peroxydisulfate (PDS) activator (CF-nZVI-JE) was prepared via in-situ loading nano zero-valent iron (nZVI) on Juncus effusus (JE) followed with wrapping a layer of cellulose film (CF). The CF-nZVI-JE had the same 3D structure as the JE, being easy to separate from aqueous solution. The loaded nZVI existed single nanoparticles with a size of 60-100 nm except chain-type agglomeration of nanoparticles due to the stabilization of JE fibers.
View Article and Find Full Text PDFThe cytochromes P450 (CYPs) represent a large gene superfamily that plays an important role in the metabolism of both exogenous and endogenous compounds. We have reported that the testis-specific Y-encoded-like proteins (TSPYLs) are novel gene transcriptional regulators. However, little is known of mechanism(s) by which TSPYLs regulate expression or the functional consequences of that regulation.
View Article and Find Full Text PDFCytochrome P450s () display significant inter-individual variation in expression, much of which remains unexplained by known single-nucleotide polymorphisms (SNPs). Testis-specific Y-encoded-like proteins (s) are transcriptional regulators for several drug-metabolizing including However, transcription factors (TFs) that might influence expression through an effect on expression are unknown. Therefore, we studied regulators of expression in hepatic cell lines and their possible SNP-dependent variation.
View Article and Find Full Text PDFThe application of patient-derived xenografts (PDX) in drug screening and testing is a costly and time-consuming endeavor. While cell lines permit extensive mechanistic studies, many human breast cancer cell lines lack patient characteristics and clinical treatment information. Establishing cell lines that retain patient's genetic and drug response information would enable greater drug screening and mechanistic studies.
View Article and Find Full Text PDFThe present study aimed to examine the psychological mechanism underlying the relationship between attachment style and intimate relationship satisfaction in women. For this purpose, a cross-sectional research design was employed in which 233 women ( = 28.16 years) who were currently in a romantic relationship completed a questionnaire that assessed attachment style, relationship satisfaction, self-esteem, and flexible goal adjustment (FGA).
View Article and Find Full Text PDFDNA Repair (Amst)
April 2021
The DNA replication stress-induced checkpoint activated through the TopBP1-ATR axis is important for maintaining genomic stability. However, the regulation of TopBP1 in DNA-damage responses remains unclear. In this study, we identify the deubiquitinating enzyme (DUB) USP13 as an important regulator of TopBP1.
View Article and Find Full Text PDFIn this study, soybean root distribution in an inter-cropping system was influenced by various environmental and biotic cues. However, it is still unknown how root development and distribution in inter-cropping responds to aboveground light conditions. Herein, soybeans were inter- and monocropped with P (phosphorus) treatments of 0 and 20 kg P ha yr (P0 and P20, respectively) in field experiment over 4 years.
View Article and Find Full Text PDFBreast cancer is the most common invasive cancer in women worldwide. Functional follow-up of breast cancer genome-wide association studies has led to the discovery of genes that regulate endocrine therapy response in a SNP- and drug-dependent manner. Here, we will present four examples in which functional genomic studies from breast cancer clinical trials led to novel pharmacogenomic insights and molecular mechanisms of selective estrogen receptor modulators and aromatase inhibitors.
View Article and Find Full Text PDFAims: Osteoporosis has been known to generally result from an imbalance between bone formation and resorption. Osteogenesis is the process of differentiation of mesenchymal stem cells (MSCs) into osteoblasts. Sirtuin6 (SIRT6) has been reported to mediate osteogenic differentiation (OD) in rat bone MSCs (rBMSCs).
View Article and Find Full Text PDF