FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma
FBXL19 is a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases and is linked to a variety of vital biological processes, such as cell proliferation, migration, and differentiation. Previous studies have identified it as an oncogene in breast cancer and glioma. However, its role in hepato...
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-11-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402308979X |
| _version_ | 1797429798000132096 |
|---|---|
| author | Min Xun Jiming Wang Qiuli Xie Bo Peng Zeyuan Li Zhengya Guo Yonglian Zeng Huizhao Su Mei Yao Lijuan Liao Yan Li Guandou Yuan Shilian Chen Songqing He |
| author_facet | Min Xun Jiming Wang Qiuli Xie Bo Peng Zeyuan Li Zhengya Guo Yonglian Zeng Huizhao Su Mei Yao Lijuan Liao Yan Li Guandou Yuan Shilian Chen Songqing He |
| author_sort | Min Xun |
| collection | DOAJ |
| description | FBXL19 is a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases and is linked to a variety of vital biological processes, such as cell proliferation, migration, and differentiation. Previous studies have identified it as an oncogene in breast cancer and glioma. However, its role in hepatocellular carcinoma (HCC) remains unclear. To comprehensively elucidate its role in tumour biology and its underlying mechanisms, a variety of sophisticated methods, including bioinformatics analysis, RNA-sequencing technique, and in vitro cell biology experiments, were used. Here, we found that FBXL19 was upregulated in patients with HCC and correlated with poor prognosis. In in vitro experiments, the specific targeting of short hairpin RNAs via lentiviruses successfully induced the knockdown of FBXL19, resulting in notable inhibition of the proliferation, migration, and invasion of HCC cells. Furthermore, FBXL19 downregulation resulted in significant induction of G0/G1 phase cell cycle arrest. Importantly, FBXL19 knockdown inhibited tumour malignant behaviour primarily by inactivating extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinases. In conclusion, this study revealed that FBXL19 was upregulated in patients with HCC, and that its expression was negatively correlated with prognosis. Thus, FBXL19 displays oncogenic properties in HCC by activating mitogen-activated protein kinase signalling. |
| first_indexed | 2024-03-09T09:18:19Z |
| format | Article |
| id | doaj.art-f2154c3af1164b3099b141e05f987963 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-09T09:18:19Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-f2154c3af1164b3099b141e05f9879632023-12-02T07:04:11ZengElsevierHeliyon2405-84402023-11-01911e21771FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinomaMin Xun0Jiming Wang1Qiuli Xie2Bo Peng3Zeyuan Li4Zhengya Guo5Yonglian Zeng6Huizhao Su7Mei Yao8Lijuan Liao9Yan Li10Guandou Yuan11Shilian Chen12Songqing He13Division of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, ChinaChongqing University FuLing Hospital, Chongqing 408099, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, ChinaDivision of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, China; Corresponding author. Division of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.Division of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China; Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi 530021, China; Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases, Nanning, Guangxi 530021, China; Corresponding author. Division of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.FBXL19 is a member of the Skp1-Cullin-F-box family of E3 ubiquitin ligases and is linked to a variety of vital biological processes, such as cell proliferation, migration, and differentiation. Previous studies have identified it as an oncogene in breast cancer and glioma. However, its role in hepatocellular carcinoma (HCC) remains unclear. To comprehensively elucidate its role in tumour biology and its underlying mechanisms, a variety of sophisticated methods, including bioinformatics analysis, RNA-sequencing technique, and in vitro cell biology experiments, were used. Here, we found that FBXL19 was upregulated in patients with HCC and correlated with poor prognosis. In in vitro experiments, the specific targeting of short hairpin RNAs via lentiviruses successfully induced the knockdown of FBXL19, resulting in notable inhibition of the proliferation, migration, and invasion of HCC cells. Furthermore, FBXL19 downregulation resulted in significant induction of G0/G1 phase cell cycle arrest. Importantly, FBXL19 knockdown inhibited tumour malignant behaviour primarily by inactivating extracellular signal-regulated protein kinase 1/2 and p38 mitogen-activated protein kinases. In conclusion, this study revealed that FBXL19 was upregulated in patients with HCC, and that its expression was negatively correlated with prognosis. Thus, FBXL19 displays oncogenic properties in HCC by activating mitogen-activated protein kinase signalling.http://www.sciencedirect.com/science/article/pii/S240584402308979XHepatocellular carcinomaFBXL19Cell proliferationMigration |
| spellingShingle | Min Xun Jiming Wang Qiuli Xie Bo Peng Zeyuan Li Zhengya Guo Yonglian Zeng Huizhao Su Mei Yao Lijuan Liao Yan Li Guandou Yuan Shilian Chen Songqing He FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma Heliyon Hepatocellular carcinoma FBXL19 Cell proliferation Migration |
| title | FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma |
| title_full | FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma |
| title_fullStr | FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma |
| title_full_unstemmed | FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma |
| title_short | FBXL19 promotes malignant behaviours by activating MAPK signalling and negatively correlates with prognosis in hepatocellular carcinoma |
| title_sort | fbxl19 promotes malignant behaviours by activating mapk signalling and negatively correlates with prognosis in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma FBXL19 Cell proliferation Migration |
| url | http://www.sciencedirect.com/science/article/pii/S240584402308979X |
| work_keys_str_mv | AT minxun fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT jimingwang fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT qiulixie fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT bopeng fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT zeyuanli fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT zhengyaguo fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT yonglianzeng fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT huizhaosu fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT meiyao fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT lijuanliao fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT yanli fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT guandouyuan fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT shilianchen fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma AT songqinghe fbxl19promotesmalignantbehavioursbyactivatingmapksignallingandnegativelycorrelateswithprognosisinhepatocellularcarcinoma |