Epigenetic changes correspond to heritable modifications of the chromatin structure, which do not involve any alteration of the DNA sequence but nonetheless affect gene expression. These mechanisms play an important role in cell differentiation, but aberrant occurrences are also associated with a number of diseases, including cancer and neural development disorders. In particular, aberrant DNA methylation induced by H. Pylori has been found to be a significant risk factor in gastric cancer. To investigate the sensitivity of different genes and cell types to this infection, a computational model of methylation in gastric crypts is developed. In this article, we review existing results from physical experiments and outline their limitations, before presenting the computational model and investigating the influence of its parameters.
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http://dx.doi.org/10.1016/j.jtbi.2010.02.040 | DOI Listing |
Zhong Nan Da Xue Xue Bao Yi Xue Ban
July 2024
Southern Hospital affiliated with Shenzhen University, Shenzhen Guangdong 518001, China.
Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with poor prognosis. RNA alternative splicing dysregulation plays a critical role in the initiation and progression of TNBC. This article systematically introduces the basic process of RNA splicing and then focuses on reviewing the aberrant alternative splicing events and their biological effects in TNBC: 1) Multiple splicing-related factors promote tumor cell proliferation and mediate chemotherapy resistance by regulating the alternative splicing of genes involved in cell survival and drug response; 2) dysregulation of splicing regulatory networks leads to altered splicing of multiple metastasis-related genes, promoting tumor invasion and metastasis; 3) aberrant alternative splicing events participate in tumor progression by affecting the expression of DNA damage repair genes; 4) dysregulation of alternative splicing is also involved in the regulation of tumor immune evasion and stem cell properties.
View Article and Find Full Text PDFBioorg Chem
December 2024
Department of Natural Products & Medicinal Chemistry, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, Telangana, India; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:
Cyclin-dependent kinases, CDK7 and CDK9 play critical roles in cancer by regulating transcriptional processes essential for cell proliferation and survival. Their dysregulation leads to aberrant gene expression, promoting oncogenic pathways and contributing to tumor growth and progression. This study aimed to identify a new chemotype for CDK7/9 inhibitors using a structure-based virtual screening approach.
View Article and Find Full Text PDFAnticancer Drugs
January 2025
The First Clinical Medical School, Lanzhou University.
This study investigated whether the neddylation inhibitor MLN4924 induces aberrant DNA methylation patterns in acute myeloid leukemia and contributes to the reactivation of tumor suppressor genes. DNA methylation profiles of Kasumi-1 and KU812 acute myeloid leukemia cell lines before and after MLN4924 treatment were generated using the 850K Methylation BeadChip. RNA sequencing was used to obtain transcriptomic profiles of Kasumi-1 cells.
View Article and Find Full Text PDFHum Genet
January 2025
John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Developmental anomalies of the hearing organ, the cochlea, are diagnosed in approximately one-fourth of individuals with congenital. The majority of patients with cochlear malformations remain etiologically undiagnosed due to insufficient knowledge about underlying genes or the inability to make conclusive interpretations of identified genetic variants. We used exome sequencing for the genetic evaluation of hearing loss associated with cochlear malformations in three probands from unrelated families deafness.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The Chinese University of Hong Kong, Hong Kong, Hong Kong.
Background: Emerging evidence strongly suggests that terminally differentiated neurons in the brain have the potential to undergo a cell cycle-like process during neuronal aging and in the presence of certain diseases. However, due to their infrequent occurrence and unpredictable distribution within the brain, the molecular characteristics and specific variations associated with these cells in different diseases are still not well understood.
Method: By taking advantage of the wealth of human brain single-nucleus RNA sequencing (snRNA-seq) datasets available in public repositories, we developed an analytical pipeline that facilitates the identification and characterization of cell cycle gene re-expressing neurons to address these questions.
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