Al-Azzam, N. | Search bioRxiv

bioRxiv2025

Multi-omics profiling reveals microenvironmental remodeling as a key driver of house dust mite-induced lung cancer progression

Chronic exposure to the common aeroallergen house dust mite (HDM) induces lung inflammation and DNA damage, but its impact on lung cancer development remains largely unexplored. Using whole-genome sequencing, RNA-seq, and DNA methylation profiling, we assessed HDM effects in lung epithelial cell lines and a mouse orthotopic lung cancer model. HDM accelerated tumor growth without altering mutational burden. Transcriptomic and epigenetic analyses revealed tissue-specific effects: in normal lung, HDM enhanced pro-inflammatory and immune activation programs, whereas in tumors it suppressed T cell responses, antigen presentation, and chemokine signaling. Immune deconvolution showed a shift toward myeloid enrichment and lymphoid suppression, with reduced cytotoxic T and NK signatures. Notably, HDM-driven tumor promotion was abolished in Il17a-/- but not Il1b-/-mice, identifying IL-17A as a critical mediator. These findings demonstrate that chronic aeroallergen exposure reshapes the lung microenvironment to promote immune suppression and accelerate lung cancer progression. HighlightsChronic house dust mite (HDM) exposure accelerates lung tumor growth through non-mutagenic, immune-mediated mechanisms. HDM activates pro-inflammatory and immune programs in normal lung tissue but suppresses antitumor T cell responses in tumors. Multi-omics profiling reveals epigenetic silencing of immune genes and a myeloid-enriched, lymphoid-deficient tumor microenvironment. HDM-driven tumor promotion depends on IL-17A but not IL-1{beta}, establishing IL-17A as a central driver of lung tumor promotion.

cancer biology↗

bioRxiv2023

Large-scale map of RNA binding protein interactomes across the mRNA life-cycle

Messenger RNAs (mRNAs) interact with RNA-binding proteins (RBPs) in diverse ribonucleoprotein complexes (RNPs) during distinct life-cycle stages for their processing and maturation. While substantial attention has focused on understanding RNA regulation by assigning proteins, particularly RBPs, to specific RNA substrates, there has been considerably less exploration leveraging protein-protein interaction (PPI) methodologies to identify and study the role of proteins in mRNA life-cycle stages. To address this gap, we generated an RNA-aware RBP-centric PPI map across the mRNA life-cycle by immunopurification (IP-MS) of [~]100 endogenous RBPs across the life-cycle in the presence or absence of RNase, augmented by size exclusion chromatography (SEC-MS). Aside from confirming 8,700 known and discovering 20,359 novel interactions between 1125 proteins, we determined that 73% of our IP interactions are regulated by the presence of RNA. Our PPI data enables us to link proteins to life-cycle stage functions, highlighting that nearly half of the proteins participate in at least two distinct stages. We show that one of the most highly interconnected proteins, ERH, engages in multiple RNA processes, including via interactions with nuclear speckles and the mRNA export machinery. We also demonstrate that the spliceosomal protein SNRNP200 participates in distinct stress granule-associated RNPs and occupies different RNA target regions in the cytoplasm during stress. Our comprehensive RBP-focused PPI network is a novel resource for identifying multi-stage RBPs and exploring RBP complexes in RNA maturation. HIGHLIGHTSO_LIAn RBP-centric RNA-aware PPI network focuses on the mRNA life-cycle in human cells C_LIO_LIPrey-prey correlation analysis assigns prey proteins to life-cycle stages, of which 536 proteins (half of the network) interact with multiple steps C_LIO_LIERH is highly connected to multiple RNPs to affect nuclear speckle organization and mRNA export C_LIO_LISplicing factor SNRNP200 interacts with stress granule proteins and has distinct RNA occupancy in the cytoplasm C_LI

systems biology↗