Tumorigenesis involves transcriptomic alterations at both gene and isoform levels. While short-read RNA-seq cann’t fully resolve isoform-level changes, long-read RNA sequencing (lrRNA-seq) overcomes this limitation. In this study, we analyzed 144 paired tumor-normal transcriptomes across ten organs using lrRNA-seq. Our pan-cancer analysis revealed convergent gene expression associated with oncogenic dedifferentiation, contrasting with variable, organ-specific isoform-level alterations. Isoform-level changes, including aberrant fusion transcripts and disrupted isoform composition, were widespread and partially linked to altered splicing factor expression. Notably, many genes showed significant isoform alterations without corresponding gene expression differences. Integrating gene and isoform-level data, we developed a pan-cancer scoring framework to identify candidate prognostic correlates and potential therapeutic targets for further validation. This framework uncovered multiple underappreciated pan-cancer susceptibility genes, such as IBSP and FANCL, whose dysregulation occurs predominantly at the isoform level. Our findings advance understanding of tumor transcriptomics and provide a resource for future biomarker and therapeutic development.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine. In recent years, it has been unveiled that N6-methyladenosine (also named m6A) modification, the most prevalent internal mRNA modification in mammalian cells, plays a pivotal role in the pathogenesis and development of IBD. m6A modification exerts on all four components of the intestinal barrier, including the intestinal mechanical barrier, intestinal chemical barrier, intestinal immunological barrier, and intestinal biological barrier. This paper reviews previous studies that focused on the role of m6A modification in IBD, aiming to elucidate the epigenetic mechanisms underlying IBD pathogenesis and progression, and offering novel perspectives for IBD diagnosis, treatment and prognosis prediction.

• Majorbio Cloud provides a one-stop proteomics platform for proteomics and multi-omics analytics.

A study led by researchers at NYU Grossman School of Medicine identified shared molecular patterns in human milk that link maternal nutrition, mammary gland biology, and infant growth.

Why do large dogs tend to live shorter lives than their smaller counterparts? According to a new study of nearly 900 dogs, the answer may be written into their epigenome. The findings reveal that larger and male dogs undergo accelerated molecular aging, with pronounced DNA methylation (DNAm) on the X chromosome and at transposable elements (TEs). Aging is a universal process, but its pace and biological mechanisms substantially differ between individuals and species. Domestic dogs offer a particularly useful model for understanding the biology of aging because their lifespans vary dramatically with body size. For example, smaller breeds can live nearly twice as long as larger breeds. Moreover, companion dogs also live in human environments, consume commercial diets, and receive routine medical care, making them a relevant translational model for studying how genetic background and environmental exposures shape aging. However, how intrinsic factors such as size and biological sex influence variation in dog aging and lifespan remains unclear. Previous research has demonstrated that DNAm is a useful indicator of biological aging, with “epigenetic clocks” offering a way to understand the factors that accelerate or decelerate biological aging.

 

Blaise Mariner and colleagues generated 1,640 methylomes from a cohort of 894 dogs in the Dog Aging Project. They combined these molecular data with detailed genetic and demographic data. Mariner et al. found that molecular aging occurs most rapidly early in a dog’s life. What’s more, larger and male dogs – both of which have shorter lifespans than their respective counterparts – age more quickly at the molecular level. The authors identified different epigenetic patterns underlying these effects. According to the findings, sex-related changes were concentrated on the X chromosome, while body-size-related changes were especially prominent in TEs, stretches of DNA that can influence genome stability and gene regulation.