ArticleJournal of experimental & clinical cancer research : CR2023
MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation.
Article in Journal of experimental & clinical cancer research : CR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- MKRN1 suppresses cuproptosis in colorectal cancer through ubiquitin-dependent regulation of SLC31A1.Biological procedures online · 2026Article
- Review
- Low expression of MKRN1 promotes leukemia cell proliferation.European journal of medical research · 2025Article
- MKRN1 degrades AGC1 to trigger chemotherapy resistance of colorectal Cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Exploring the Role of the TGF-β Signaling Pathway in Colorectal Precancerous Polyps Biochemical Genetics.Biochemical genetics · 2025Review
- The emerging role of E3 ubiquitin ligases and deubiquitinases in metabolic dysfunction-associated steatotic liver disease.Journal of translational medicine · 2025Review
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Correction: MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation.Journal of experimental & clinical cancer research : CR · 2025Article
- Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025Review
- Ubiquitination and ALL: Identifying FBXO8 as a prognostic biomarker and therapeutic target.Frontiers in immunology · 2025Article
- The Role of Redox Environment in Tumors.Current medicinal chemistry · 2025Review
- Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies.Cancer biology & medicine · 2024Review
- Article
- MKRN1 regulates the expression profiles and transcription factor activity in HeLa cells inhibition suppresses cervical cancer cell progression.Scientific reports · 2024Article
- Identification and validation of the nicotine metabolism-related signature of bladder cancer by bioinformatics and machine learning.Frontiers in immunology · 2024Article
- Correction: MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation.Journal of experimental & clinical cancer research : CR · 2023Article
- Makorin Ring Finger Protein 1 Inhibits Cell Proliferation in Renal Angiomyolipoma via the ERK/MAPK Signaling Pathway.Kidney diseases (Basel, Switzerland)Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe Makorin ring finger protein 1 (MKRN1) gene, also called RNF61, is located on the long arm of chromosome 7 and is a member of the RING finger protein family. The E3 ubiquitin ligase MKRN1 is closely linked to tumour development, but the exact mechanism needs to be elucidated. In this study, we aimed to investigate the specific mechanism and role of MKRN1 in colorectal cancer (CRC) development.
methodsMKRN1 expression in CRC was analysed using the Cancer Cell Line Encyclopaedia and the Cancer Genome Atlas (TCGA) databases. Rectal tumour tissues were frozen to explore the MKRN1 expression in CRC and its clinical significance. The impact of MKRN1 on CRC cell proliferation and migration was observed using CCK8, colony formation, wound healing, and transwell assays. A combination of MKRN1 quantitative proteomics, ubiquitination modification omics analysis, and a string of in vitro and in vivo experiments revealed the potential mechanisms by which MKRN1 regulates CRC metastasis.
resultsMKRN1 expression was significantly elevated in CRC tissues compared to paracancerous tissues and was positively linked with prognosis (P < 0.01). MKRN1 downregulation inhibits CRC cell proliferation, migration, and invasion. Conversely, MKRN1 overexpression promotes the proliferation, migration, and invasion of CRC cells. Mechanistically, MKRN1 induces epithelial-mesenchymal transition (EMT) in CRC cells via ubiquitination and degradation of Smad nuclear-interacting protein 1 (SNIP1). Furthermore, SNIP1 inhibits transforming growth factor-β (TGF-β) signalling, and MKRN1 promotes TGF-β signalling by degrading SNIP1 to induce EMT in CRC cells. Finally, using conditional knockout mice, intestinal lesions and metastatic liver microlesions were greatly reduced in the intestinal knockout MKRN1 group compared to that in the control group.
conclusionsHigh MKRN1 levels promote TGF-β signalling through ubiquitination and degradation of SNIP1, thereby facilitating CRC metastasis, and supporting MKRN1 as a CRC pro-cancer factor. The MKRN1/SNIP1/TGF-β axis may be a potential therapeutic target in CRC.
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