Over the past decade, multiple research studies have focused on using miRNA expression in colorectal cancer (CRC) pathogenesis.

Objective. The insulin receptor substrate 2 (IRS2) is phosphorylated by the tyrosine kinase activity of the insulin receptor and the insulin-like growth factor I (IGF-1) receptor upon receptor stimulation. It mediates insulin signaling controlling metabolism as well as cell proliferation and invasion in tumors. Hypoxia and endoplasmic reticulum (ER) stress are significant factors in regulating the growth of malignant tumors including glioblastoma. The present study aims to investigate the regulation of the IRS2 gene expression in normal human astrocytes and U87MG glioblastoma cells by hypoxia and ER stress in the context of the native stress hormone hydrocortisone, which is widely used for the co-treatment of glioblastoma. Methods. The normal human astrocytes (line NHA/TS) and U87MG glioblastoma cells were used. Hypoxia was introduced by the HIF1A prolyl hydroxylase inhibitor dimethyloxalylglycine (DMOG), which mimics the effects of hypoxia under normoxic conditions. Tunicamycin and thapsigargin were used for the induction of ER stress. Hydrocortisone-water soluble BioReagent, suitable for cell culture (cyclodextrin-encapsulated hydrocortisone) was used. Cells were treated with DMOG, tunicamycin, thapsigargin, and hydrocortisone for 4 h. RNA was extracted with TRIzol reagent. IRS2 gene expression was examined by quantitative real-time RT-PCR and normalized to beta-actin mRNA. Results. It was found that hypoxia decreased the IRS2 gene expression in normal human astrocytes, but upregulated it in glioblastoma cells. At the same time, hydrocortisone did not significantly change the expression of this gene in both normal astrocytes and glioblastoma cells. However, hypoxia in combination with hydrocortisone strongly increased IRS2 gene expression in both cell types. Tunicamycin decreased the expression of the IRS2 gene in normal astrocytes, but increased it in glioblastoma cells and this effect of tunicamycin was not significantly altered by hypoxia in both cell types. At the same time, thapsigargin did not significantly alter the expression of the IRS2 gene in normal astrocytes, but it strongly upregulated it in glioblastoma cells. Hypoxia modified the effect of thapsigargin on this gene expression in both cell types, but by different ways: decreased in normal astrocytes and increased in glioblastoma cells. In addition, the impact of tunicamycin and thapsigargin on IRS2 gene expression was significantly upregulated by hydrocortisone in normal astrocytes and especially in glioblastoma cells. At the same time, the combined effect of hypoxia and hydrocortisone enhanced the expression of the IRS2 gene in tunicamycintreated normal astrocytes, especially in the glioblastoma cells. Hydrocortisone also increased the effect of hypoxia on this gene expression in thapsigargin-treated normal astrocytes and decreased it in glioblastoma cells. Conclusion. Our findings provide evidence that hypoxic regulation of IRS2 gene expression is modified by inducers of ER stress and hydrocortisone, but differently in normal astrocytes and glioblastoma cells and that the combined effect of hypoxia with ER stress and hydrocortisone greatly enhanced this gene expression in both cell types, especially in the glioblastoma cells.

Polygenic risk scores (PRS), a measure that sums multiple common genetic susceptibility variants into a single burden measure, can help identify individuals at higher risk for colorectal cancer (CRC). Consequently, there is growing interest in its potential use to guide screening practices, despite the current lack of evidence-based guidelines on the clinical utility of PRS models. Therefore, there is a need to understand the potential challenges and factors associated with PRS use in primary care settings. This qualitative study explores the perceptions of healthcare providers with PRS information to guide CRC screening decisions in the primary care setting. Using an exploratory approach, we conducted semi-structured interviews with 10 healthcare providers. The socioecological model guided the development of the interview questions. Transcripts were coded based on emergent themes. A total of seven themes were identified in this study, and each was organized using the socioecological model at the individual, interpersonal, community, and organizational levels. One key finding was the limited knowledge of PRS and the distinction between PRS and genetic testing for high-penetrant germline mutations. Providers shared the need for training, education, and comprehensive clinical guidelines for the use of PRS. This study provides insights to better optimize genetic education, testing, access, and care for improved CRC screening in at-risk individuals.

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition characterized by highly variable presentation, making reproductive decision-making and pregnancy care particularly complex. While previous research has focused largely on clinical outcomes, little is known about how healthcare professionals (HCPs) provide care and communicate with patients during this process. This qualitative study explores the views and experiences of HCPs in providing reproductive and pregnancy-related care for individuals with NF1. Fifteen semi-structured interviews were conducted with genetic counselors, NF specialist nurses, and clinical geneticists in the UK. Reflexive thematic analysis was used to analyze the data. HCPs described supporting informed reproductive choices as central to their role, but this was often complicated by the unpredictable nature of NF1 and varying levels of patient understanding. They emphasized the importance of discussing reproductive choices early, yet found it particularly difficult to offer clear guidance when patients had mild symptoms themselves or drew on diverse family experiences to interpret risk. These challenges were further compounded by systemic barriers, such as limited consultation time, lack of standardized communication tools, and insufficient training. This study highlights the need for more structured and consistent communication practices to support patients with NF1 during reproductive and pregnancy care. A simplified, context-specific visual tool informed by the theoretical domains framework (TDF) may enhance counseling practice.

Polymerase theta (Pol θ) is a DNA repair factor that has drawn much recent interest as a target for cancer therapy, since its inhibition is well-tolerated in most cells but is lethal in cancers deficient in breast cancer-associated (BRCA) genes ("synthetic lethality"). Its normal biological functions, as well as how these functions change in BRCA-deficient cancers, are only recently becoming clear, however. We review here recent progress in our understanding of the cellular regulatory mechanisms at work in determining if Pol θ sees DNA damage. At the molecular scale Pol θ then must notably see and repair diverse classes of damage, including (at least) conventional double strand breaks (made by e.g. ionizing radiation), as well as several types of damage associated with replication stress. We speculate on the mechanisms that could explain this flexibility.

Esophageal squamous cell carcinoma (ESCC) imposes a heavy disease burden in China, accounting for over 50% of global cases and approximately 301,000 annual deaths. Current prognostic markers inadequately predict recurrence in early-stage patients. This study investigates microRNA-107 (miR-107) as a novel prognostic biomarker for ESCC.

AT-rich interaction domain 1A (ARID1A), is frequently mutated in cancer, leading to loss-of-function and posing challenges to therapeutic targeting. This study aimed to systematically explore epigenetic regulation of ARID1A, specifically promoter hypermethylation, in gastric cancer (GC) and its functional/immunological consequences.

Non-small cell lung cancer (NSCLC) is one of the most frequent cancer types and is responsible for the majority of cancer-related deaths all over the world. N-acetyltransferase 10 (NAT10) has been reported to regulate N4-acetylcytidine (ac4C) modification of downstream mRNAs through certain pathways, thereby promoting the progression of diverse tumors, including lung cancer. However, the role and potential mechanism of NAT10 on NSCLC development is still unclear. In this study, GEPIA and TNMplot databases were applied to analyze Forkhead box A1 (FOXA1) expression in lung cancer patients. FOXA1 and NAT10 expression were determined using real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell viability, proliferation, apoptosis, invasion, migration, and stemness were detected using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, Transwell, wound healing, and sphere formation assays. The abundance of ac4C on FOXA1 mRNA was measured using acRIP-qPCR. Their interaction was verified using RIP and dual-luciferase reporter assays. After JASPAR analysis, the binding between FOXA1 and NAT10 promoter was predicted and then verified using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. FOXA1 expression was increased in NSCLC tissues and cells, and its knockdown repressed NSCLC cell viability, proliferation, migration, invasion, stemness, and induced apoptosis in vitro. In mechanism, NAT10 maintained FOXA1 mRNA stability in an ac4C-dependent manner. Moreover, FOXA1 was also a transcription factor of NAT10 and increased the transcriptional activity of NAT10 via binding to its promoter region. These findings created a positive feedback cycle to facilitate NSCLC progression. This study elucidated the pivotal role of abnormal activation of the FOXA1/NAT10 positive feedback loop in the malignant progression of NSCLC, thereby uncovering novel prognostic factors and therapeutic targets in NSCLC.

Microsatellite instability (MSI) and tumor mutational burden (TMB) are crucial biomarkers in gastric (GC) and colorectal cancer (CRC), yet their conventional sequencing-based detection is costly and time-consuming. Since only ~20% of patients are MSI-high or TMB-high and likely to benefit from immunotherapy, expensive genomic testing is often unjustified. This study developed a deep learning framework to predict MSI and TMB status directly from routinely available Hematoxylin and Eosin (H&E)-stained whole-slide images, leveraging fused nuclear segmentation features to improve accuracy. Using samples from TCGA (350 GC and 376 CRC for MSI; 400 GC and 387 CRC for TMB), image features were extracted with CLAM and nuclear features with Hover-Net. These features were combined via Multimodal Compact Bilinear Pooling and utilized in six distinct deep learning models. By fusing the nucleus segmentation features, the model increased area under the receiver operating characteristic curve (AUC) by 1%-3% and recall by 5%-11% in five-fold cross-validation, significantly outperforming models that relied solely on image features. External validation on a CRC dataset from the China-Japan Friendship hospital further validated the model's robustness, achieving an AUC of 0.81 and a recall of 0.80 for MSI prediction. Additionally, notable differences in cellular composition were observed across cancer types and clinical groups, emphasizing the pivotal role of cellular features in cancer development. These findings highlight the advantages of integrating H&E-stained image features with nuclear segmentation data and advanced deep learning techniques to improve predictive accuracy and reduce the cost of MSI/TMB testing, potentially advancing personalized cancer treatment strategies.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by oligo-anovulation, hyperandrogenism, and polycystic ovarian morphology. While its etiology is multifactorial, genetic susceptibility plays a key role in its pathophysiology.

Patients with advanced ovarian cancer (AOC) who are BRCA wild-type (BRCAwt) or exhibit low loss of heterozygosity (LOH-low) typically face a poor prognosis and have limited therapeutic options. Pembrolizumab plus chemotherapy followed by maintenance with or without olaparib (PCO or PC) brings new hope to these patients. However, the substantial financial burden associated with these regimens necessitates a thorough cost-effectiveness evaluation.

Colorectal cancer (CRC) is an aggressive malignancy with high mortality, and the identification of upstream regulators of stemness represents a critical step toward developing more effective targeted therapies. This study aimed to define the role of NR5A2 in CRC, particularly in the context of cancer stem cells (CSCs).

Most mutant adenomatous polyposis coli (APC) gene produced truncated APC protein (Trunc-APC), which has been shown to function as an oncogene in colorectal cancer (CRC) pathogenesis; however, its role in modulating innate immune responses within tumor cells remains unexplored.

Despite therapeutic advances, multiple myeloma (MM) remains incurable, especially in relapsed/refractory (R/R) disease. B-cell maturation antigen (BCMA)-targeted CAR-T therapy, exemplified by FDA-approved agents like ide-cel and cilta-cel, offers promise, yet accessibility barriers necessitate local production.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder characterized by hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. Despite increasing recognition of immune and metabolic dysregulation in its pathogenesis, the cell-specific molecular mechanisms, particularly within granulosa cells, remain poorly understood. This study aimed to elucidate the transcriptomic landscape and regulatory pathways of granulosa cells in PCOS using integrative bioinformatics and experimental validation.

The mechanisms underlying the development and prognosis of hepatocellular carcinoma (HCC) differ between dogs and humans. Although genetic alterations can cause carcinogenesis, the genetic alterations in canine HCC may differ from those observed in human HCC. In humans, various signaling pathways, oncogenes, and tumor suppressor genes are associated with HCC oncogenesis. Immune cells have been reported to be associated with prognosis. In canine HCC, the genes related to oncogenesis and prognosis remain unclear. Therefore, in this study, we used RNA sequencing to comprehensively evaluate abnormally expressed genes and infer immune cell composition in canine HCC.

Although non-muscle-invasive bladder cancer (NMIBC) frequently recurs and progresses despite BCG therapy, cellular mechanisms behind this remain unclear. Understanding the dynamics within the tumor microenvironment (TME) and identifying pathways associated with BCG resistance are crucial for improving NMIBC treatment.

The global trend toward delayed childbearing has led to an increased use of fertility treatment, including in vitro fertilization (IVF) and hormonal medications. Concerns regarding the potential impact of these interventions on breast cancer risk, particularly among high-risk women with a pathogenic variant in the BRCA1 or BRCA2 genes remains an important clinical concern.

Gastric cancer (GC) is still imposing a severe threat to human health. An increasing number of studies have found that neural activity plays an important role in the tumor microenvironment. However, the clinical implications of nerve-related genes (NRGs) remain largely unexplored.

This study aimed to determine whether the presence of intraductal carcinoma of the prostate or invasive cribriform carcinoma correlates with homologous recombination repair or mismatch repair gene alterations in patients with prostate cancer who have not undergone prior systemic treatment.