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Gene signatures derived from transcriptomic-causal networks stratify colorectal cancer patients for effective targeted therapy.
Commun Med (Lond)
January 2025
Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.
Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.
Identifying ADME-related gene signature for immune landscape and prognosis in KIRC by single-cell and spatial transcriptome analysis.
Sci Rep
January 2025
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
Kidney renal clear cell carcinoma (KIRC) is the most prevalent subtype of kidney cancer. Although multiple therapeutic agents have been proven effective in KIRC, their clinical application has been hindered by a lack of reliable biomarkers. This study focused on the prognostic value and function of drug absorption, distribution, metabolism, and excretion- (ADME-) related genes (ARGs) in KIRC to enhance personalized therapy.
View Article and Find Full Text PDFThe most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is an intronic GC repeat expansion in C9orf72. The repeats undergo bidirectional transcription to produce sense and antisense repeat RNA species, which are translated into dipeptide repeat proteins (DPRs). As toxicity has been associated with both sense and antisense repeat-derived RNA and DPRs, targeting both strands may provide the most effective therapeutic strategy.
View Article and Find Full Text PDFKLF5 loss sensitizes cells to ATR inhibition and is synthetic lethal with ARID1A deficiency.
Nat Commun
January 2025
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
ATR plays key roles in cellular responses to DNA damage and replication stress, a pervasive feature of cancer cells. ATR inhibitors (ATRi) are in clinical development for treating various cancers, including those with high replication stress, such as is elicited by ARID1A deficiency, but the cellular mechanisms that determine ATRi efficacy in such backgrounds are unclear. Here, we have conducted unbiased genome-scale CRISPR screens in ARID1A-deficient and proficient cells treated with ATRi.
View Article and Find Full Text PDFThe Diverse Roles of Long Non-Coding RNA HOTTIP in Breast and Gynecological Cancer Progression.
Curr Mol Med
January 2025
Department of Laboratory, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Long non-coding RNAs (lncRNAs) play vital roles in the development and progression of various tumors through multiple mechanisms. Among these, HOTTIP (HOXA transcript at the distal tip) stands out as an intriguing candidate with diverse functions in several malignancies, including breast cancer and gynecologic cancers such as ovarian, cervical, and endometrial cancers, which are significant global health concerns. HOTTIP interacts with key signaling pathways associated with these cancers, including Wnt/β-catenin, PI3K/AKT, and MEK/ERK pathways, enhancing their activation and downstream effects.
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