ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/082/SRR22484282/SRR22484282_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/079/SRR22484279/SRR22484279_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/081/SRR22484281/SRR22484281_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/082/SRR22484282/SRR22484282_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/079/SRR22484279/SRR22484279_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/080/SRR22484280/SRR22484280_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/081/SRR22484281/SRR22484281_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR224/080/SRR22484280/SRR22484280_1.fastq.gzprimaryOK200GenomicsNanjing First Hospitalhttps://www.ebi.ac.uk/ena/browser/view/PRJNA907315Homo sapiens5-fluorouracil (5‑FU) based chemotherapy is the first-line chemotherapy scheme for CRC, whereas acquired drug resistance poses a huge obstacle to curing CRC patients and the mechanism is still obscure. METTL14 is a core subunit of the m6A methyltransferase complex and has been reported to regulate the drug resistance of cancers. Here, we demonstrated that METTL14 is significantly downregulated in 5-FU-resistant CRC and METTL14 overexpression inhibits the proliferation and 5-FU resistance of CRC cells in vitro and in vivo. In addition, we found that MIB1 catalyzes the K63-linked ubiquitination of METTL14 and induces its degradation through the autolysosome pathway, while AURKA-mediated phosphorylation enhances METTL14 stability by inhibiting its ubiquitination. Moreover, we first discovered that METTL14 functions in 5-FU-resistant CRC cells by directly participating in the translation initiation of non-m6A-modified mRNAs independently of METTL3, rather than cooperating with METTL3 to methylate adenosine residues of targets. Further analysis indicated that METTL14 regulates the cell cycle process in 5-FU-resistant CRC cells. Collectively, our study not only identified METTL14 as a potential therapeutic target for 5-FU resistance in CRC but also revealed a novel translation-facilitating role of METTL14. Overall design: METTL14 overexpression plasmids and negative control plasmids were transfected into 5-FU-resistant HCT-8 cells, respectively. Then cells were treated with 100ug/mL CHX and implemented to the Ribosome-sequencing. Experiments were performed twice independently.ENAprotein translation, Post Translational Amino Acid Modification, Colorectal Neoplasm, 5 FU Medac, Post-Translational Protein Modifications, Colorectal Cancer, Footprintings, Carac, Ribo-seq, Neoplasms, Capture, Fluorouracil Monosodium Salt, Tumor, Haemato FU, Protein Processing, autosomal dominant, 5 Fluorouracil Biosyn, Fluorouracil-GRY, Flurodex, Posttranslational, Translation, Colorectal, colorectal cancer, Translation Profilings, Fluorouracil Mononitrate, Ribosome Footprinting, Ribo-Seq, Post Translational Modification, 2, Post-Translational Modifications, Fluoro Uracile ICN, Profilings, Post Translational, Fluorouracil Potassium Salt, Colorectal Tumors, Modification, Post-Translational Protein, Ribosome-Bound tRNA Captures, 5-Fluorouracil-Biosyn, Post-Translational, Ribosome-Bound., Efudex, Ribosome-Bound tRNA Capture, Colorectal Carcinomas, 5 HU Hexal, Colorectal Tumor, tRNA Capture, Posttranslational Protein Processing, 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tRNA Captures, Ribosome Bound tRNA Capture, Protein Modification, Translating Ribosome Affinity Purification, Fluoro-Uracile ICN, Carcinomas, large bowel cancer, Ribosome, 5FU, 5-FU Lederle, Fluorouracilo Ferrer Far, Post Translational Protein Processing, mKIAA1627, Processing, susceptibility to, Colorectal Carcinoma, Adrucil, Cancers, Fluoruracil, Ribosome-Bound, cancer of large bowel, Ribosome Footprintings, Fluorouracil, Post Translational Protein Modification, Fluoroplex, colon cancer, Amino Acid Modification, 5-HU Hexal, protein synthesis, fluorouracilum, G430022H21Rik, Haemato-FU, Captures, Post-Translational Protein Processing, ribosome footprinting, cancer of the large bowel, Posttranslational Modifications, Fluorouracil GRY, cancer of large intestine, fluorouracilo, Ribo-seq assay, Posttranslational Modificationprotein translation, Post Translational Amino Acid Modification, Colorectal Neoplasm, 5 FU Medac, Post-Translational Protein Modifications, Colorectal Cancer, Footprintings, Carac, Ribo-seq, Neoplasms, Capture, Fluorouracil Monosodium Salt, Tumor, Haemato FU, Protein Processing, autosomal dominant, 5 Fluorouracil Biosyn, Fluorouracil-GRY, Flurodex, Posttranslational, Translation, Colorectal, colorectal cancer, Translation Profilings, Fluorouracil Mononitrate, Ribosome Footprinting, Ribo-Seq, Post Translational Modification, 2, Post-Translational Modifications, Fluoro Uracile ICN, Profilings, Post Translational, Fluorouracil Potassium Salt, Colorectal Tumors, Modification, Post-Translational Protein, Ribosome-Bound tRNA Captures, 5-Fluorouracil-Biosyn, Post-Translational, Ribosome-Bound., Efudex, Ribosome-Bound tRNA Capture, Colorectal Carcinomas, 5 HU Hexal, Colorectal Tumor, tRNA Capture, Posttranslational Protein Processing, Fluracedyl, Fluorouracile Dakota, large intestine cancer, Protein Modifications, Fluorouracile, cancer of the large intestine, Post-Translational Amino Acid Modification, Posttranslational Amino Acid Modification, 3H)-Pyrimidinedione, Posttranslational Protein, 5-fluoro-, 5-Fluoropyrimidine-2, Dakota, somatic mutation, colorectal (colon or rectal) cancer, 5-FU, 5 FU Lederle, Tumors, Cancer, Translation Profiling, Post-Translational Modification, Carcinoma, Profiling, protein anabolism, Fluorouracil Monopotassium Salt, 5-Fluorouracil, protein biosynthetic process, ARTSeq, fluorouracil, Ribofluor, Ribosome Profilings, Modifications, 5-Fluoracil, 5-FU Medac, Post-Translational Protein Modification, ribosome profiling, active mRNA translation sequencing, Onkofluor, 5 Fluorouracil, RGD1304822, Ribosome-Bound tRNA, Post Translational Modifications, 4-dione, Efudix, protein formation, Neoplasm, Neofluor, Footprinting, protein biosynthesis, ribosomal profiling, 4(1H, CRC, Colorectal Cancers, tRNA Captures, Ribosome Bound tRNA Capture, Protein Modification, Translating Ribosome Affinity Purification, Fluoro-Uracile ICN, Carcinomas, large bowel cancer, Ribosome, 5FU, 5-FU Lederle, Fluorouracilo Ferrer Far, Post Translational Protein Processing, mKIAA1627, Processing, susceptibility to, Colorectal Carcinoma, Adrucil, Cancers, Fluoruracil, Ribosome-Bound, cancer of large bowel, Ribosome Footprintings, Fluorouracil, Post Translational Protein Modification, Fluoroplex, colon cancer, Amino Acid Modification, 5-HU Hexal, protein synthesis, fluorouracilum, G430022H21Rik, Haemato-FU, Captures, Post-Translational Protein Processing, ribosome footprinting, cancer of the large bowel, Posttranslational Modifications, Fluorouracil GRY, cancer of large intestine, fluorouracilo, Ribo-seq assay, Posttranslational ModificationfalseThe post-translational modifications and translation-regulatory role of METTL14 in 5-fluorouracil-resistant colorectal cancer [Ribo-seq]The post-translational modifications and translation-regulatory role of METTL14 in 5-fluorouracil-resistant colorectal cancer [Ribo-seq]2025-09-242023-12-02PRJNA907315GSE2191729606