ArticleThe EMBO journal2023
Role of PCIF1-mediated 5'-cap N6-methyladeonsine mRNA methylation in colorectal cancer and anti-PD-1 immunotherapy.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 50 citations in OpenAlex.
- Blocking the mCellular & molecular immunology · 2026Article
- METTL4 enhances GLI1 translation through mJournal of advanced research · 2026Article
- Blocking the mNature communications · 2026Article
- Engineering Bisubstrates to Target mChemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- RNA modifications in cancer and their detection: a review.Japanese journal of clinical oncology · 2026Review
- Tumor Electric Field Therapy Inhibits Epithelial-Mesenchymal Transition, Invasion, and Migration of Glioblastoma by Targeting the c-FOS/CXCL14 Axis.CNS neuroscience & therapeutics · 2026Article
- Programmable RNA NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The m6Am methyltransferase PCIF1 promotes osteogenic differentiation of mesenchymal stem cells through stabilization of Wnt-related transcripts.PLoS biology · 2026Article
- Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- Emerging nano-immunotherapeutic strategies achieve metastatic colorectal cancer precision therapy.Journal of nanobiotechnology · 2026Review
- Outer membrane vesicles fromFrontiers in microbiology · 2026Article
- RNA modifications in health and disease: from mechanistic insights to therapeutic applications.Precision clinical medicine · 2025Review
- The WW domain presents a promising target for the development of PCIF1 agonists in the treatment of glioma.NPJ precision oncology · 2025Article
- New strategies to enhance the efficacy of PD-1/PD-L1 inhibitors in treating microsatellite stable colorectal cancer.Future oncology (London, England) · 2025Review
- N6-adenosine methyltransferase METTL4 is a potential prognostic biomarker and associates with cell cycle regulation and immune infiltration in glioma.Translational cancer research · 2025Article
- STAT1-IFITM3 promotes autophagy in epithelial cells to controlLife science alliance · 2025Article
- SERBP1-PCIF1 complex-controlled m6Am modification in glutamatergic neurons of the primary somatosensory cortex is required for neuropathic pain in mice.Nature communications · 2025Article
- The mechanisms and clinical significance of CD8Cancer biology & medicine · 2025Review
- Introduction of human mMicrobial cell factories · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Adenosine N6-methylation (m6A) and N6,2'-O-dimethylation (m6Am) are regulatory modifications of eukaryotic mRNAs. m6Am formation is catalyzed by the methyl transferase phosphorylated CTD-interacting factor 1 (PCIF1); however, the pathophysiological functions of this RNA modification and PCIF1 in cancers are unclear. Here, we show that PCIF1 expression is upregulated in colorectal cancer (CRC) and negatively correlates with patient survival. CRISPR/Cas9-mediated depletion of PCIF1 in human CRC cells leads to loss of cell migration, invasion, and colony formation in vitro and loss of tumor growth in athymic mice. Pcif1 knockout in murine CRC cells inhibits tumor growth in immunocompetent mice and enhances the effects of anti-PD-1 antibody treatment by decreasing intratumoral TGF-β levels and increasing intratumoral IFN-γ, TNF-α levels, and tumor-infiltrating natural killer cells. We further show that PCIF1 modulates CRC growth and response to anti-PD-1 in a context-dependent mechanism with PCIF1 directly targeting FOS, IFITM3, and STAT1 via m6Am modifications. PCIF1 stabilizes FOS mRNA, which in turn leads to FOS-dependent TGF-β regulation and tumor growth. While during immunotherapy, Pcif1-Fos-TGF-β, as well as Pcif1-Stat1/Ifitm3-IFN-γ axes, contributes to the resistance of anti-PD-1 therapy. Collectively, our findings reveal a role of PCIF1 in promoting CRC tumorigenesis and resistance to anti-PD-1 therapy, supporting that the combination of PCIF1 inhibition with anti-PD-1 treatment is a potential therapeutic strategy to enhance CRC response to immunotherapy. Finally, we developed a lipid nanoparticles (LNPs) and chemically modified small interfering RNAs (CMsiRNAs)-based strategy to silence PCIF1 in vivo and found that this treatment significantly reduced tumor growth in mice. Our results therefore provide a proof-of-concept for tumor growth suppression using LNP-CMsiRNA to silence target genes in cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.