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Enhancers regulate multiple genes via higher-order chromatin structures, and they further affect cancer progression. Epigenetic changes in cancer cells activate several cancer-specific enhancers that are silenced in normal cells. These cancer-specific enhancers are potential therapeutic targets of cancer. However, the functions and regulation networks of colorectal-cancer-specific enhancers are still unknown. In this study, we profile colorectal-cancer-specific enhancers and reveal their regulation network through the analysis of HiChIP data that were derived from a colorectal cancer cell line and Hi-C and RNA-seq data that were derived from tissue samples by in silico analysis and in vitro experiments. Enhancer-promoter loops in colorectal cancer cells containing colorectal-cancer-specific enhancers are involved in more than 50% of the topological associated domains (TADs) changed in colorectal cancer cells compared to normal colon cells. In addition, colorectal-cancer-specific enhancers interact with 152 genes that are significantly and highly expressed in colorectal cancer cells. These colorectal-cancer-specific enhancer target genes include , , , and . We propose that the regulation network of colorectal-cancer-specific enhancers plays an important role in the progression of colorectal cancer.
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http://dx.doi.org/10.3390/ijms22158337 | DOI Listing |
Adv Sci (Weinh)
August 2025
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 210023, China.
Adoptive cell therapies for solid tumors face persistent challenges from poor tumor infiltration and immunosuppressive microenvironment. To overcome these limitations, a clinically scalable platform is developed to generate chimeric antigen receptor macrophages (CAR-HMs) from tamoxifen-regulated immortalized Hoxb8-transduced myeloid progenitors, achieving >95% CAR transduction efficiency and 60-fold expansion within 10 days. Engineered with a colorectal cancer-specific anti-carcinoembryonic antigen (CEA) CAR, these FcγRI-CAR-HMs demonstrated potent tumoricidal activity (>80% CRC cell lysis in vitro), deep tissue penetration (>100 µm in 3D tumor spheroids), and significant therapeutic efficacy (≈89% tumor regression in vivo).
View Article and Find Full Text PDFFront Microbiol
August 2024
Central Laboratory, Weifang People's Hospital, Shandong Second Medical University, Weifang, China.
Introduction: Accumulating evidence has supported that gut microbiota and metabolite profiles play indispensable roles in the pathogenesis of colorectal cancer (CRC), which ranks as the third most common cancer and the second leading cause of cancer-related deaths worldwide. However, alterations in tumoral or circulating microbiomes in CRC remain incompletely understood. It has been well-documented that tissue or serum microbiomes with low microbial biomass could be screened by use of 2bRAD sequencing for microbiome (2bRAD-M) at the species resolution.
View Article and Find Full Text PDFJ Transl Med
June 2024
Department of coloproctology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Background: The molecular complexity of colorectal cancer poses a significant challenge to the clinical implementation of accurate risk stratification. There is still an urgent need to find better biomarkers to enhance established risk stratification and guide risk-adapted treatment decisions.
Methods: we systematically analyzed cancer dependencies of 17 colorectal cancer cells and 513 other cancer cells based on genome-scale CRISPR-Cas9 knockout screens to identify colorectal cancer-specific fitness genes.
J Immunother Cancer
May 2024
Proton Cancer, China Medical University Hospital, Taichung, Taiwan
Background: Cancer-intrinsic type I interferon (IFN-I) production triggered by radiotherapy (RT) is mainly dependent on cytosolic double-stranded DNA (dsDNA)-mediated cGAS/STING signaling and increases cancer immunogenicity and enhances the antitumor immune response to increase therapeutic efficacy. However, cGAS/STING deficiency in colorectal cancer (CRC) may suppress the RT-induced antitumor immunity. Therefore, we aimed to evaluate the importance of the dsRNA-mediated antitumor immune response induced by RT in patients with CRC.
View Article and Find Full Text PDFCancer Epidemiol Biomarkers Prev
November 2023
The Lundquist Institute, Torrance, California.
Background: The few cohort studies examining oophorectomy and colorectal cancer risk provide mixed results. Therefore, we examined this issue in Women's Health Initiative Observational Study participants.
Methods: A total of 71,312 postmenopausal women were followed for 22.