Musa, M. | bioRxiv Science

bioRxiv2025

RBPMS as a novel marker for cancer-associated fibroblasts in distinguishing left and right colorectal cancer sidedness

BackgroundColorectal cancer (CRC) can be classified into left-sided (LCRC) and right-sided CRC (RCRC). These CRC entities present different molecular phenotypes and prognosis. Accumulation of cancer-associated fibroblasts (CAFs) reflects poor prognosis and recurrence of CRC. CAF-cancer cell crosstalk regulates fibroblast activation and drives CRC progression, facilitated via secretomes including TGF{beta}1. CAF-cancer cell interplay according to colon sidedness have yet to be fully investigated due to the lack of robust marker for CAF. ObjectiveTo explore a novel CAF marker in differentiating the mechanisms of LCRC and RCRC. MethodsCAFs from cancerous tissues of LCRC and RCRC patients and normal fibroblasts from adjacent normal colon tissues were established. Profiling of these fibroblasts were performed. Gene expression of the fibroblasts was analyzed via Affymetrix Clariom S (Human) assay, validated using Western blot. The effect of TGF{beta}1 on protein expression of fibroblasts was also studied. Epithelial cancer cell lines were used as controls. ResultsFibroblast profiling showed differences in morphology and proliferation between CAFs and NFs, and pro-proliferative effect of CAFs on CRC cells. Molecular analyses revealed RNA-binding protein with multiple splicing (RBPMS) to be differentially expressed between CAFs and NFs from left and right colon. RBPMS was significantly upregulated in CAFs from LCRC compared to their respective NFs. In contrast, RBPMS was downregulated in CAFs from RCRC compared to their NFs (p<0.05). Furthermore, TGF{beta}1 induced RBPMS expression in CAFs and NFs from the left colon, whereas it suppressed RBPMS expression in fibroblasts from right colon. CAFs from LCRC resembled myCAFs with myofibroblast-related expression signatures, whereas those from RCRC signified iCAFs with inflammatory marker expression. ConclusionThis study highlighted RBPMS as a novel CAF marker in differentiating the mechanisms between LCRC and RCRC. This finding may be utilized in CAF-targeted therapy for CRC.

molecular biology↗

bioRxiv2021

Functional peroxisomes are required for heat shock-induced hormesis in Caenorhabditis elegans

Exact mechanisms of heat shock induced lifespan extension, while documented across species, are still not well understood. Here we put forth evidence that fully functional peroxisomes are required for the activation of the canonical heat shock response and heat-induced hormesis in C. elegans. While during heat shock the HSP-70 chaperone is strongly upregulated in the wild-type (WT) as well as in the absence of peroxisomal catalase ({Delta}ctl-2 mutant), the small heat shock proteins display modestly increased expression in the mutant. Nuclear localization of HSF-1 is reduced in the{Delta} ctl-2 mutant. In addition, heat-induced lifespan extension, observed in the WT, is absent in the{Delta} ctl-2 mutant. Activation of the antioxidant response, the pentose phosphate pathway and increased triglyceride content are the most prominent changes observed during heat shock in the WT worm, but not in the{Delta} ctl-2 mutant. Involvement of peroxisomes in the cell-wide response to transient heat shock reported here gives new insight into the role of organelle communication in the organisms stress response.

cell biology↗