RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma
Abstract Background Accumulated evidence suggests that RING finger proteins (RNFs) are involved in the carcinogenesis of cancers. However, RNF38, a member of the RNF protein family, has not been studied in nasopharyngeal carcinoma (NPC). Methods RNF38 expression was analyzed by RT-PCR, Western blott...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-022-09641-x |
| _version_ | 1828747821451313152 |
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| author | Cheng Lin Meifang Li Na Lin Jingfeng Zong Jianji Pan Yunbin Ye |
| author_facet | Cheng Lin Meifang Li Na Lin Jingfeng Zong Jianji Pan Yunbin Ye |
| author_sort | Cheng Lin |
| collection | DOAJ |
| description | Abstract Background Accumulated evidence suggests that RING finger proteins (RNFs) are involved in the carcinogenesis of cancers. However, RNF38, a member of the RNF protein family, has not been studied in nasopharyngeal carcinoma (NPC). Methods RNF38 expression was analyzed by RT-PCR, Western blotting and Immunohistochemistry. Biological functions of RNF38 were evaluated by cell growth, colony formation, apoptosis, migration and invasion assays in vitro. Xenograft growth and lung metastasis models were conducted to investigate the effect of RNF38 in vivo. Liquid chromatography coupled with tandem mass spectrometry, co-immunoprecipitation, and CHX assay were implemented to detect the interaction among RNF38 and ACTN4. Results RNF38 was significantly downregulated in NPC cells and tissues. Immunohistochemistry implied that loss of RNF38 was an independent prognostic factor for poor outcomes of NPC patients. Gain- and loss-of-function experiments showed that RNF38 inhibited proliferation and metastasis in NPC in vitro and in vivo. Upregulation of RNF38 promoted apoptosis of NPC cells to etoposide but not cisplatin. ACTN4 was upregulated in NPC and negatively correlated with RNF38. Mechanistic investigations suggested that RNF38 inactivates the NF-𝛋B and ERK1/2 signaling pathways by inducing ubiquitination and degradation of ACTN4. RNF38 suppress the development of NPC by interacting with ACTN4. Conclusions RNF38 plays a potential cancer suppressor gene role in NPC tumorigenesis and is a prognostic biomarker in NPC. |
| first_indexed | 2024-04-14T04:48:10Z |
| format | Article |
| id | doaj.art-36e78b4e4b9646ca8b25a79b088e42b5 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-14T04:48:10Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-36e78b4e4b9646ca8b25a79b088e42b52022-12-22T02:11:22ZengBMCBMC Cancer1471-24072022-05-0122111310.1186/s12885-022-09641-xRNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinomaCheng Lin0Meifang Li1Na Lin2Jingfeng Zong3Jianji Pan4Yunbin Ye5Department of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalDepartment of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalDepartment of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalDepartment of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalDepartment of Radiation Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer HospitalLaboratory of Immuno-Oncology, Fujian Cancer HospitalAbstract Background Accumulated evidence suggests that RING finger proteins (RNFs) are involved in the carcinogenesis of cancers. However, RNF38, a member of the RNF protein family, has not been studied in nasopharyngeal carcinoma (NPC). Methods RNF38 expression was analyzed by RT-PCR, Western blotting and Immunohistochemistry. Biological functions of RNF38 were evaluated by cell growth, colony formation, apoptosis, migration and invasion assays in vitro. Xenograft growth and lung metastasis models were conducted to investigate the effect of RNF38 in vivo. Liquid chromatography coupled with tandem mass spectrometry, co-immunoprecipitation, and CHX assay were implemented to detect the interaction among RNF38 and ACTN4. Results RNF38 was significantly downregulated in NPC cells and tissues. Immunohistochemistry implied that loss of RNF38 was an independent prognostic factor for poor outcomes of NPC patients. Gain- and loss-of-function experiments showed that RNF38 inhibited proliferation and metastasis in NPC in vitro and in vivo. Upregulation of RNF38 promoted apoptosis of NPC cells to etoposide but not cisplatin. ACTN4 was upregulated in NPC and negatively correlated with RNF38. Mechanistic investigations suggested that RNF38 inactivates the NF-𝛋B and ERK1/2 signaling pathways by inducing ubiquitination and degradation of ACTN4. RNF38 suppress the development of NPC by interacting with ACTN4. Conclusions RNF38 plays a potential cancer suppressor gene role in NPC tumorigenesis and is a prognostic biomarker in NPC.https://doi.org/10.1186/s12885-022-09641-xNasopharyngeal carcinomaRNF38GrowthMetastasisUbiquitinationACTN4 |
| spellingShingle | Cheng Lin Meifang Li Na Lin Jingfeng Zong Jianji Pan Yunbin Ye RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma BMC Cancer Nasopharyngeal carcinoma RNF38 Growth Metastasis Ubiquitination ACTN4 |
| title | RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma |
| title_full | RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma |
| title_fullStr | RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma |
| title_full_unstemmed | RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma |
| title_short | RNF38 suppress growth and metastasis via ubiquitination of ACTN4 in nasopharyngeal carcinoma |
| title_sort | rnf38 suppress growth and metastasis via ubiquitination of actn4 in nasopharyngeal carcinoma |
| topic | Nasopharyngeal carcinoma RNF38 Growth Metastasis Ubiquitination ACTN4 |
| url | https://doi.org/10.1186/s12885-022-09641-x |
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