Ring finger 220 promotes the stemness and progression of colon cancer cells via Ubiquitin specific peptidase 22-BMI1 axis

Yan, Jianwen; Tan, Mengxi; Yu, Lin; Jin, Xichao; Li, Yangcheng

doi:10.1080/21655979.2021.2003664

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…At their N-terminus, RING finger proteins have a RING structural domain that interacts with ubiquitin and transports it to the protein substrate. RNF proteins play a function in the growth of various cancers [ 33 ]. For example, RNF126 is linked to early breast cancer metastasis and promotes breast cancer cell proliferation and development [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation

Zhang,

Li,

Liu

et al. 2023

J Exp Clin Cancer Res

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Background The 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. Methods MKRN1 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. Results MKRN1 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. Conclusions High 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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Section: Discussionmentioning

confidence: 99%

MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation

Zhang,

Li,

Liu

et al. 2023

J Exp Clin Cancer Res

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“…Research has demonstrated that RNF2 expression is signi cantly increased in tumour cells of gastric cancer patients, and knockdown of RNF2 inhibits tumour cell viability by affecting the cell cycle 34 . In both in vivo and in vitro experiments, it was discovered that RNF220 is signi cantly upregulated in colorectal cancer 35 . Furthermore, cell scratch and plate clone formation experiments demonstrated that RNF220 promotes the proliferation, migration, and invasion of colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, cell scratch and plate clone formation experiments demonstrated that RNF220 promotes the proliferation, migration, and invasion of colorectal cancer cells. Subsequently, a subcutaneous xenograft tumour mouse model was established, which revealed that RNF220 promotes tumour growth in vivo 35 . This upregulation promoted invasion and metastasis of both types of cancer cells by increasing the epithelial mesenchyme.…”

Section: Discussionmentioning

confidence: 99%

Ring Finger Protein 141 (RNF141) Mediates Resistance to Sorafenib in Hepatocellular Carcinoma and Its Mechanisms

Chen,

Xie,

Liu

et al. 2024

Preprint

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OBJECTIVE: This study aims to investigate the expression of ring finger protein 141 (RNF141) in hepatocellular carcinoma, its role in sorafenib resistance, and its possible mechanism. MATERIALS AND METHODS: The expression of RNF141 in the cancer and corresponding para-cancerous liver tissues of patients with hepatocellular carcinoma was detected using Immunohistochemistry (IHC) staining and Western blot. The liver cancer cell line (SMMC7721) and the sorafenib-resistant liver cancer cell line (SMMC7721-S) were transfected with lentivirus to overexpress or silence RNF141, and the IC50 of sorafenib was then measured. Flow cytometry and TUNEL staining were used to detect changes in cell apoptosis before and after overexpression and silencing of RNF141. The levels of the proliferation marker protein, proliferating cell nuclear antigen (PCNA), and the apoptosis marker protein, Cleaved PARP, were detected using Western blot. Additionally, a tumor xenograft model was constructed by subcutaneously injecting RNF141-knockdown SMMC7721 and SMMC7721-S stable transfected strains into nude mice. The study observed and recorded the shape, size, and weight of tumors in each group. Hematoxylin and Eosin (HE) staining and immunohistochemistry (IHC) staining of PCNA were used to verify the effect of RNF141 on the efficacy of sorafenib in vivo. Finally, digital gene expression profiling (DGE) was used to further screen the signaling pathways involved in RNF141-mediated HCC resistance to sorafenib. RESULTS: The study found that the expression of RNF141 was significantly higher in hepatocellular carcinoma tissues compared to corresponding paracancerous tissues (P<0.01), as shown by IHC staining results and Western blot analysis. Hepatocellular carcinoma cell lines that overexpress and silence RNF141, as well as sorafenib-resistant hepatocellular carcinoma cell lines, were successfully constructed. Overexpression of RNF141 resulted in an increase in the IC50 value of sorafenib in hepatocellular carcinoma cells, as well as the ability to resist sorafenib-induced proliferation inhibition and apoptosis. Conversely, silencing RNF141 resulted in a decrease in the IC50 value of sorafenib, and further enhanced sorafenib-induced proliferation inhibition and apoptosis. The digital gene expression profiling results were analysed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) signalling pathway enrichment analysis, which revealed a significant enrichment of the proteasome signalling pathway. CONCLUSION: RNF141 may contribute to sorafenib resistance in hepatocellular carcinoma through the proteasome signaling pathway.

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“…A study reported that ring finger 220 (RNF220) is upregulated in CRC tissues and cell lines and is associated with increased CRC stemness and tumor growth in vivo . This oncogenic activity of RNF220 is indirectly mediated by USP22[ 49 ]. USP22 also stabilizes ZRANB1 (zinc finger RANBP2-type containing 1), a positive regulator of the Wnt/β-catenin pathway, and promotes SC-like features of CRC cells[ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review

Al-Balushi,

Al Marzouqi,

Tavoosi

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Colorectal cancer (CRC) is the third most frequent and the second most fatal cancer. The search for more effective drugs to treat this disease is ongoing. A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic strategies. Ubiquitin-specific peptidases (USPs), the largest group of the deubiquitinase protein family, have long been implicated in various cancers. There have been numerous studies on the role of USPs in CRC; however, a comprehensive view of this role is lacking. AIM To provide a systematic review of the studies investigating the roles and functions of USPs in CRC. METHODS We systematically queried the MEDLINE (via PubMed), Scopus, and Web of Science databases. RESULTS Our study highlights the pivotal role of various USPs in several processes implicated in CRC: Regulation of the cell cycle, apoptosis, cancer stemness, epithelial–mesenchymal transition, metastasis, DNA repair, and drug resistance. The findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in CRC. The dysregulation of USPs in CRC contributes to drug resistance through multiple mechanisms. CONCLUSION Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

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Ring finger 220 promotes the stemness and progression of colon cancer cells via Ubiquitin specific peptidase 22-BMI1 axis

Cited by 6 publications

References 27 publications

MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation

MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation

Ring Finger Protein 141 (RNF141) Mediates Resistance to Sorafenib in Hepatocellular Carcinoma and Its Mechanisms

Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review

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