<i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma
Migration and invasion play crucial roles in the progression of hepatocellular carcinoma (HCC), but the underlying mechanisms are not clear. Analysis of clinical samples indicates that SQSTM1/p62 is highly expressed in HCC and seriously affects the prognosis of patients. Subsequently, we showed that...
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MDPI AG
2023-04-01
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| author | Jinghua Lu Yipei Ding Wanqiu Zhang Yuanyuan Qi Jin Zhou Naihan Xu Yaou Zhang Weidong Xie |
| author_facet | Jinghua Lu Yipei Ding Wanqiu Zhang Yuanyuan Qi Jin Zhou Naihan Xu Yaou Zhang Weidong Xie |
| author_sort | Jinghua Lu |
| collection | DOAJ |
| description | Migration and invasion play crucial roles in the progression of hepatocellular carcinoma (HCC), but the underlying mechanisms are not clear. Analysis of clinical samples indicates that SQSTM1/p62 is highly expressed in HCC and seriously affects the prognosis of patients. Subsequently, we showed that <i>SQSTM1/p62</i> knockout using the CRISPR/Cas9 system led to impaired migration and invasion of HCC, upregulated Keap1, and promoted the inhibitory effect of Keap1 on Nrf2. Then, the inactivation of Nrf2 inhibited the expression of matrix metalloproteinases (MMPs), thus attenuating the migration and invasion of HCC. We also found that <i>SQSTM1/p62</i> knockout significantly inhibited migration and invasion in a lung metastasis model of nude mice with HCC. Furthermore, we found that cisplatin not only significantly inhibited the expression of SQSTM1/p62 but also slowed down the migration and invasion of HCC, while the inflammatory microenvironment accelerated the migration and invasion of HCC. These results suggest for the first time that <i>SQSTM1/p62</i> knockout inhibits the migration and invasion of HCC through the Keap1/Nrf2/MMP2 signaling pathway. SQSTM1/p62 may be developed into a key drug target to regulate the migration and invasion of HCC cells. |
| first_indexed | 2024-03-11T04:22:35Z |
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| id | doaj.art-c6fb00c0bec4418c8afca5e93637cd89 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T04:22:35Z |
| publishDate | 2023-04-01 |
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| spelling | doaj.art-c6fb00c0bec4418c8afca5e93637cd892023-11-17T22:43:13ZengMDPI AGCells2073-44092023-04-01129123810.3390/cells12091238<i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular CarcinomaJinghua Lu0Yipei Ding1Wanqiu Zhang2Yuanyuan Qi3Jin Zhou4Naihan Xu5Yaou Zhang6Weidong Xie7State Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaState Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaState Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaState Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaInstitute for Ocean Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaState Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaState Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaState Key Laboratory of Chemical Oncogenomics, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, ChinaMigration and invasion play crucial roles in the progression of hepatocellular carcinoma (HCC), but the underlying mechanisms are not clear. Analysis of clinical samples indicates that SQSTM1/p62 is highly expressed in HCC and seriously affects the prognosis of patients. Subsequently, we showed that <i>SQSTM1/p62</i> knockout using the CRISPR/Cas9 system led to impaired migration and invasion of HCC, upregulated Keap1, and promoted the inhibitory effect of Keap1 on Nrf2. Then, the inactivation of Nrf2 inhibited the expression of matrix metalloproteinases (MMPs), thus attenuating the migration and invasion of HCC. We also found that <i>SQSTM1/p62</i> knockout significantly inhibited migration and invasion in a lung metastasis model of nude mice with HCC. Furthermore, we found that cisplatin not only significantly inhibited the expression of SQSTM1/p62 but also slowed down the migration and invasion of HCC, while the inflammatory microenvironment accelerated the migration and invasion of HCC. These results suggest for the first time that <i>SQSTM1/p62</i> knockout inhibits the migration and invasion of HCC through the Keap1/Nrf2/MMP2 signaling pathway. SQSTM1/p62 may be developed into a key drug target to regulate the migration and invasion of HCC cells.https://www.mdpi.com/2073-4409/12/9/1238migrationinvasionhepatocellular carcinomaSQSTM1/p62 |
| spellingShingle | Jinghua Lu Yipei Ding Wanqiu Zhang Yuanyuan Qi Jin Zhou Naihan Xu Yaou Zhang Weidong Xie <i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma Cells migration invasion hepatocellular carcinoma SQSTM1/p62 |
| title | <i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma |
| title_full | <i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma |
| title_fullStr | <i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma |
| title_full_unstemmed | <i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma |
| title_short | <i>SQSTM1/p62</i> Knockout by Using the CRISPR/Cas9 System Inhibits Migration and Invasion of Hepatocellular Carcinoma |
| title_sort | i sqstm1 p62 i knockout by using the crispr cas9 system inhibits migration and invasion of hepatocellular carcinoma |
| topic | migration invasion hepatocellular carcinoma SQSTM1/p62 |
| url | https://www.mdpi.com/2073-4409/12/9/1238 |
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