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Background: In recent years, the emphasis has shifted to understanding the role of N1-methyladenosine (m1A) in tumor progression as little is known about its regulatory effect on mRNA and its role in the metastasis of colorectal cancer (CRC).
Methods: We performed methylated RNA immunoprecipitation sequencing of tumor tissues and tumor-adjacent normal tissues from three patients with CRC to determine the m1A profile of mRNA in CRC. The expression of diaphanous-related formin 3 (DIAPH3) and its correlation with clinicopathological characteristics of CRC were evaluated using immunohistochemistry and online datasets. The role of DIAPH3 in the migration and invasion of CRC cells was evaluated using wound healing assay, Transwell assay and xenograft metastatic model. The downstream targets of DIAPH3 were screened using mass spectrometry. By co-transfecting DIAPH3 siRNA and a keratin 19 (KRT19) ectopic plasmid into CRC cells, the role of DIAPH3-KRT19 signaling axis was confirmed.
Results: The mRNA level of DIAPH3 and its m1A modifications increased simultaneously in the CRC tissues. In addition, high DIAPH3 expression in CRC tissues is significantly associated with metastasis and progression to an advanced stage. After the knockdown of DIAPH3, the migration and invasion capabilities of CRC cells suffered a notable decline, which could be rescued by overexpressing KRT19. In addition, the proteasome inhibitor MG132 could block the degradation of KRT19 induced by DIAPH3 silencing.
Conclusions: Our study reveals that DIAPH3 mRNA was modified in CRC cells by m1A methylation. Silencing DIAPH3 suppresses the migration and invasion of CRC cells, potentially through the proteasome-dependent degradation of downstream KRT19.
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http://dx.doi.org/10.1007/s10585-024-10323-0 | DOI Listing |
Dig Dis Sci
September 2025
Department of Gastroenterology and Hepatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Background And Aims: Liver metastasis significantly contributes to poor survival in patients with colorectal cancer (CRC), posing therapeutic challenges due to limited understanding of its mechanisms. We aimed to identify a potential target critical for CRC liver metastasis.
Methods: We analyzed the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases and identified EphrinA3 (EFNA3) as a potential clinically relevant target.
Biomed Environ Sci
August 2025
Gastrointestinal Disease Centre, Hebei Key Laboratory of Colorectal Cancer Precision Diagnosis and Treatment, The First Hospital of Hebei Medical University, Shijiazhuang 050031, Hebei, China.
Objective: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC).
Methods: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram.
JTO Clin Res Rep
October 2025
Clinical Research Center (CRC), Medical Pathology Center (MPC), Cancer Early Detection and Treatment Center (CEDTC), and Translational Medicine Research Center (TMRC), Chongqing University Three Gorges Hospital, Wanzhou District, Chongqing, People's Republic of China.
NUT carcinoma is a rare and highly aggressive malignancy characterized by rapid progression, resistance to conventional therapies, and an extremely poor prognosis. This report presents a 36-year-old patient with stage IIIB primary pulmonary NUT carcinoma who achieved remarkable clinical outcomes with NHWD-870 monotherapy, a novel BET inhibitor. After just 1 month of treatment, imaging revealed a partial response, and a complete response was achieved within 5 months.
View Article and Find Full Text PDFNat Cell Biol
September 2025
NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, Harbin Medical University, Harbin, China.
The colon exhibits higher propensity for tumour development than ileum. However, the role of immune microenvironment differences in driving this disparity remains unclear. Here, by comparing paired ileum and colon samples from patients with colorectal cancer (CRC) and healthy donors, we identified ileum-enriched CD160CD8 T cells with previously unrecognized characteristics, including resistance to terminal exhaustion and strong clonal expansion.
View Article and Find Full Text PDFApoptosis
September 2025
State Key Laboratory of Resource Insects, Medical Research Institute, Southwest University, Chongqing, 400715, China.
Colorectal cancer (CRC) is one of the most common and lethal malignancies worldwide, with treatment failure often attributed to chemoresistance and evasion of apoptosis. Cathayanon E (CE), a natural chalcone derivative isolated from Morus alba, has shown anticancer potential, but its role and mechanism in CRC remain largely unexplored. In this study, CE significantly inhibited CRC cell proliferation and induced apoptosis both in vitro and in vivo.
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