More and more studies indicated that extracellular vesicles (EVs) carrying miRNAs have been potential biomarkers of various cancers including colorectal cancer (CRC). This study aims to explore the function of miR-224-5p carried by EVs derived from cancer-associated fibroblasts (CAFs) in CRC. Here, we found that miR-224-5p was highly expressed while SLC4A4 was lowly expressed in CRC cells. Moreover, dual-luciferase reporter gene assay testified that miR-224-5p targeted SLC4A4. The expression of miR-224-5p in CAFs-derived EVs was found to be elevated. It was also testified that CAFs-derived EVs could transfer miR-224-5p into CRC cells. miR-224-5p in CAFs-derived EVs facilitated the proliferation, migration, invasion and anti-apoptosis of CRC cells. Overexpressing miR-224-5p increased the proliferative, migratory and invasive abilities of CRC cells and inhibit CRC cell apoptosis, while overexpressing SLC4A4 caused the opposite result. Research in vitro and in vivo further indicated that miR-224-5p promoted CRC cell progression via binding to its downstream target gene SLC4A4. Rescue assay also demonstrated that overexpressing miR-224-5p reversed the inhibitory effect of overexpressed SLC4A4 on cancer cell growth. In addition, in vivo assay identified that high level of miR-224-5p promoted the growth of cancer cells in mice in vivo. In conclusion, we explored the effect of miR-224-5p in CRC, which helps for further exploration of new methods for CRC targeted therapy.
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http://dx.doi.org/10.1093/carcin/bgab055 | DOI Listing |
J Exp Clin Cancer Res
January 2025
Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy.
Background: Bacterial toxins are emerging as promising hallmarks of colorectal cancer (CRC) pathogenesis. In particular, Cytotoxic Necrotizing Factor 1 (CNF1) from E. coli deserves special consideration due to the significantly higher prevalence of this toxin gene in CRC patients with respect to healthy subjects, and to the numerous tumor-promoting effects that have been ascribed to the toxin in vitro.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Background: Tumor microenvironment (TME), particularly immune cell infiltration, programmed cell death (PCD) and stress, has increasingly become a focal point in colorectal cancer (CRC) treatment. Uncovering the intricate crosstalk between these factors can enhance our understanding of CRC, guide therapeutic strategies, and improve patient prognosis.
Methods: We constructed an immune-related cell death and stress (ICDS) prognostic model utilizing machine learning methodologies.
Cell Death Differ
January 2025
Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Hyperactivation of the YAP/TEAD transcriptional complex in cancers facilitates the development of an immunosuppressive tumor microenvironment. Herein, we observed that the transcription factor SP1 physically interacts with and stabilizes the YAP/TEAD complex at regulatory genomic loci in colorectal cancer (CRC). In response to serum stimulation, PKCζ (protein kinase C ζ) was found to phosphorylate SP1 and enhance its interaction with TEAD4.
View Article and Find Full Text PDFNPJ Syst Biol Appl
January 2025
Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, CA, 90089, USA.
Cancer-associated fibroblasts (CAFs) play a key role in metabolic reprogramming and are well-established contributors to drug resistance in colorectal cancer (CRC). To exploit this metabolic crosstalk, we integrated a systems biology approach that identified key metabolic targets in a data-driven method and validated them experimentally. This process involved a novel machine learning-based method to computationally screen, in a high-throughput manner, the effects of enzyme perturbations predicted by a computational model of CRC metabolism.
View Article and Find Full Text PDFAnn Rheum Dis
January 2025
Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York, USA. Electronic address:
Objectives: This study aims to elucidate the microbial signatures associated with autoimmune diseases, particularly systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), compared with colorectal cancer (CRC), to identify unique biomarkers and shared microbial mechanisms that could inform specific treatment protocols.
Methods: We analysed metagenomic datasets from patient cohorts with six autoimmune conditions-SLE, IBD, multiple sclerosis, myasthenia gravis, Graves' disease and ankylosing spondylitis-contrasting these with CRC metagenomes to delineate disease-specific microbial profiles. The study focused on identifying predictive biomarkers from species profiles and functional genes, integrating protein-protein interaction analyses to explore effector-like proteins and their targets in key signalling pathways.
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