USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis
Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with strong invasiveness and poor prognosis. Previous studies have demonstrated the significant role of USP14 in various solid tumors. However, the role of USP14 in the regulation of HCC development and progression remain...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-02-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-024-12009-y |
| _version_ | 1797274314678992896 |
|---|---|
| author | Nannan Zhang Hui Zhang Xiaobing Yang Qiang Xue Quhui Wang Renan Chang Lirong Zhu Zhong Chen Xiancheng Liu |
| author_facet | Nannan Zhang Hui Zhang Xiaobing Yang Qiang Xue Quhui Wang Renan Chang Lirong Zhu Zhong Chen Xiancheng Liu |
| author_sort | Nannan Zhang |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with strong invasiveness and poor prognosis. Previous studies have demonstrated the significant role of USP14 in various solid tumors. However, the role of USP14 in the regulation of HCC development and progression remains unclear. Methods We discovered through GEO and TCGA databases that USP14 may play an important role in liver cancer. Using bioinformatics analysis based on the Cancer Genome Atlas (TCGA) database, we screened and identified USP14 as highly expressed in liver cancer. We detected the growth and metastasis of HCC cells promoted by USP14 through clone formation, cell counting kit 8 assay, Transwell assay, and flow cytometry. In addition, we detected the impact of USP14 on the downstream protein kinase B (AKT) and epithelial-mesenchymal transition (EMT) pathways using western blotting. The interaction mechanism between USP14 and HK2 was determined using immunofluorescence and coimmunoprecipitation (CO-IP) experiments. Results We found that sh-USP14 significantly inhibits the proliferation, invasion, and invasion of liver cancer cells, promoting apoptosis. Further exploration revealed that sh-USP14 significantly inhibited the expression of HK2. Sh-USP14 can significantly inhibit the expression of AKT and EMT signals. Further verification through immunofluorescence and CO-IP experiments revealed that USP14 co-expressed with HK2. Further research has found that USP14 regulates the glycolytic function of liver cancer cells by the deubiquitination of HK2. USP14 regulates the autophagy function of liver cancer cells by regulating the interaction between SQSTM1/P62 and HK2. Conclusions Our results indicate that USP14 plays a crucial role in the carcinogenesis of liver cancer. We also revealed the protein connections between USP14, HK2, and P62 and elucidated the potential mechanisms driving cancer development. The USP14/HK2/P62 axis may be a new therapeutic biomarker for the diagnosis and treatment of HCC. |
| first_indexed | 2024-03-07T14:56:37Z |
| format | Article |
| id | doaj.art-8eaa683ca65c49d5b0eadd94e6971910 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-07T14:56:37Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-8eaa683ca65c49d5b0eadd94e69719102024-03-05T19:23:49ZengBMCBMC Cancer1471-24072024-02-0124111510.1186/s12885-024-12009-yUSP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axisNannan Zhang0Hui Zhang1Xiaobing Yang2Qiang Xue3Quhui Wang4Renan Chang5Lirong Zhu6Zhong Chen7Xiancheng Liu8Medical College of Nantong UniversityDepartment of Radiation Oncology, Affiliated Hospital of Nantong UniversityDepartment of General Surgery, Huaian Hospital of Huaian CityDepartment of Radiation Oncology, Affiliated Hospital of Nantong UniversityDepartment of General Surgery, Affiliated Hospital of Nantong UniversityDepartment of General Surgery, Affiliated Hospital of Nantong UniversityDepartment of General Surgery, Affiliated Hospital of Nantong UniversityDepartment of General Surgery, Affiliated Hospital of Nantong UniversityDepartment of Radiation Oncology, Affiliated Hospital of Nantong UniversityAbstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor with strong invasiveness and poor prognosis. Previous studies have demonstrated the significant role of USP14 in various solid tumors. However, the role of USP14 in the regulation of HCC development and progression remains unclear. Methods We discovered through GEO and TCGA databases that USP14 may play an important role in liver cancer. Using bioinformatics analysis based on the Cancer Genome Atlas (TCGA) database, we screened and identified USP14 as highly expressed in liver cancer. We detected the growth and metastasis of HCC cells promoted by USP14 through clone formation, cell counting kit 8 assay, Transwell assay, and flow cytometry. In addition, we detected the impact of USP14 on the downstream protein kinase B (AKT) and epithelial-mesenchymal transition (EMT) pathways using western blotting. The interaction mechanism between USP14 and HK2 was determined using immunofluorescence and coimmunoprecipitation (CO-IP) experiments. Results We found that sh-USP14 significantly inhibits the proliferation, invasion, and invasion of liver cancer cells, promoting apoptosis. Further exploration revealed that sh-USP14 significantly inhibited the expression of HK2. Sh-USP14 can significantly inhibit the expression of AKT and EMT signals. Further verification through immunofluorescence and CO-IP experiments revealed that USP14 co-expressed with HK2. Further research has found that USP14 regulates the glycolytic function of liver cancer cells by the deubiquitination of HK2. USP14 regulates the autophagy function of liver cancer cells by regulating the interaction between SQSTM1/P62 and HK2. Conclusions Our results indicate that USP14 plays a crucial role in the carcinogenesis of liver cancer. We also revealed the protein connections between USP14, HK2, and P62 and elucidated the potential mechanisms driving cancer development. The USP14/HK2/P62 axis may be a new therapeutic biomarker for the diagnosis and treatment of HCC.https://doi.org/10.1186/s12885-024-12009-yHepatocellular carcinomaDouble quinone enzymesUSP14 |
| spellingShingle | Nannan Zhang Hui Zhang Xiaobing Yang Qiang Xue Quhui Wang Renan Chang Lirong Zhu Zhong Chen Xiancheng Liu USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis BMC Cancer Hepatocellular carcinoma Double quinone enzymes USP14 |
| title | USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis |
| title_full | USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis |
| title_fullStr | USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis |
| title_full_unstemmed | USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis |
| title_short | USP14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the HK2/AKT/P62 axis |
| title_sort | usp14 exhibits high expression levels in hepatocellular carcinoma and plays a crucial role in promoting the growth of liver cancer cells through the hk2 akt p62 axis |
| topic | Hepatocellular carcinoma Double quinone enzymes USP14 |
| url | https://doi.org/10.1186/s12885-024-12009-y |
| work_keys_str_mv | AT nannanzhang usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT huizhang usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT xiaobingyang usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT qiangxue usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT quhuiwang usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT renanchang usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT lirongzhu usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT zhongchen usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis AT xianchengliu usp14exhibitshighexpressionlevelsinhepatocellularcarcinomaandplaysacrucialroleinpromotingthegrowthoflivercancercellsthroughthehk2aktp62axis |