The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression
Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigate...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.7165 |
| _version_ | 1797205631043633152 |
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| author | Qi Wang Yuxi Huang Yu Zhu Wenlong Zhang Binfeng Wang Xuefeng Du Qiqiang Dai Fabiao Zhang Zheping Fang |
| author_facet | Qi Wang Yuxi Huang Yu Zhu Wenlong Zhang Binfeng Wang Xuefeng Du Qiqiang Dai Fabiao Zhang Zheping Fang |
| author_sort | Qi Wang |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigated. METTL5, an 18S rRNA methyltransferase, is abnormally high in HCC. But its biological function and prognostic significance in HCC remain largely unelucidated. This study aimed to investigate the role of METTL5 in HCC progression, and elucidate its possible molecular mechanisms in HCC via transcriptome sequencing, providing new insights for identifying new HCC prognostic markers and therapeutic targets. Methods The METTL5 expression in HCC and paracancerous tissues was analyzed using HCC immunohistochemical microarrays and bioinformatic retrieval methods to correlate METTL5 with clinicopathological features and survival prognosis. We constructed a METTL5 knockdown hepatocellular carcinoma cell line model and an animal model to determine the effect of METTL5 on hepatocellular carcinoma progression. Subsequently, RNA sequencing was performed to analyze the molecular mechanism of METTL5 in HCC based on the sequencing results, and relevant experiments were performed to verify it. Results We found that METTL5 expression was elevated in hepatocellular carcinoma tissues and correlated with poor patient prognosis, and in the analysis of clinicopathological features showed a correlation with TNM staging. In hepatocellular carcinoma cell lines with knockdown of METTL5, the malignant biological behavior was significantly reduced both in vitro and in vivo. Based on the sequencing results as well as the results of GO functional enrichment analysis and KEGG pathway enrichment analysis, we found that METTL5 could promote the generation and release of neutrophil extracellular capture network (NETs) and might further accelerate the progression of HCC. Conclusion The m6A methyltransferase METTL5 is overexpressed in hepatocellular carcinoma (HCC) and correlates with poor prognosis. METTL5 accelerates malignant progression of HCC by promoting generation and release of the neutrophil extracellular traps (NETs) network, providing new insights for clinical biomarkers and immunotherapeutic targets in HCC prognosis. |
| first_indexed | 2024-04-24T08:54:11Z |
| format | Article |
| id | doaj.art-42dc7c2dcf05428fa6be72831dbd5f23 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-24T08:54:11Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-42dc7c2dcf05428fa6be72831dbd5f232024-04-16T08:48:34ZengWileyCancer Medicine2045-76342024-04-01137n/an/a10.1002/cam4.7165The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progressionQi Wang0Yuxi Huang1Yu Zhu2Wenlong Zhang3Binfeng Wang4Xuefeng Du5Qiqiang Dai6Fabiao Zhang7Zheping Fang8Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Wenzhou Medical University Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Wenzhou Medical University Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Linhai Zhejiang ChinaDepartment of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province Wenzhou Medical University Linhai Zhejiang ChinaAbstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, it has a poor prognosis due to its highly invasive and metastatic nature. Consequently, identifying effective prognostic markers and potential therapeutic targets has been extensively investigated. METTL5, an 18S rRNA methyltransferase, is abnormally high in HCC. But its biological function and prognostic significance in HCC remain largely unelucidated. This study aimed to investigate the role of METTL5 in HCC progression, and elucidate its possible molecular mechanisms in HCC via transcriptome sequencing, providing new insights for identifying new HCC prognostic markers and therapeutic targets. Methods The METTL5 expression in HCC and paracancerous tissues was analyzed using HCC immunohistochemical microarrays and bioinformatic retrieval methods to correlate METTL5 with clinicopathological features and survival prognosis. We constructed a METTL5 knockdown hepatocellular carcinoma cell line model and an animal model to determine the effect of METTL5 on hepatocellular carcinoma progression. Subsequently, RNA sequencing was performed to analyze the molecular mechanism of METTL5 in HCC based on the sequencing results, and relevant experiments were performed to verify it. Results We found that METTL5 expression was elevated in hepatocellular carcinoma tissues and correlated with poor patient prognosis, and in the analysis of clinicopathological features showed a correlation with TNM staging. In hepatocellular carcinoma cell lines with knockdown of METTL5, the malignant biological behavior was significantly reduced both in vitro and in vivo. Based on the sequencing results as well as the results of GO functional enrichment analysis and KEGG pathway enrichment analysis, we found that METTL5 could promote the generation and release of neutrophil extracellular capture network (NETs) and might further accelerate the progression of HCC. Conclusion The m6A methyltransferase METTL5 is overexpressed in hepatocellular carcinoma (HCC) and correlates with poor prognosis. METTL5 accelerates malignant progression of HCC by promoting generation and release of the neutrophil extracellular traps (NETs) network, providing new insights for clinical biomarkers and immunotherapeutic targets in HCC prognosis.https://doi.org/10.1002/cam4.7165hepatocellular carcinomaimmune infiltrationm6AMETTL5prognostic |
| spellingShingle | Qi Wang Yuxi Huang Yu Zhu Wenlong Zhang Binfeng Wang Xuefeng Du Qiqiang Dai Fabiao Zhang Zheping Fang The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression Cancer Medicine hepatocellular carcinoma immune infiltration m6A METTL5 prognostic |
| title | The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression |
| title_full | The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression |
| title_fullStr | The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression |
| title_full_unstemmed | The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression |
| title_short | The m6A methyltransferase METTL5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression |
| title_sort | m6a methyltransferase mettl5 promotes neutrophil extracellular trap network release to regulate hepatocellular carcinoma progression |
| topic | hepatocellular carcinoma immune infiltration m6A METTL5 prognostic |
| url | https://doi.org/10.1002/cam4.7165 |
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