Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway
Objective To explore the effect of myotubularin-related protein 6 (MTMR6) on the invasion of hepatocellular carcinoma cell line HepG2 and the potential molecular mechanism. Methods By analyzing the sequencing results of liver cancer tissues and adjacent tissues in Gene Expression Omnibus (GEO) datab...
| Main Authors: | , , |
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| Format: | Article |
| Language: | zho |
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Editorial Office of Journal of Army Medical University
2024-02-01
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| Series: | 陆军军医大学学报 |
| Subjects: | |
| Online Access: | http://aammt.tmmu.edu.cn/html/202304051.htm |
| _version_ | 1797315584001572864 |
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| author | LIANG Xiao CHEN Hongyu PENG Xueqin |
| author_facet | LIANG Xiao CHEN Hongyu PENG Xueqin |
| author_sort | LIANG Xiao |
| collection | DOAJ |
| description | Objective To explore the effect of myotubularin-related protein 6 (MTMR6) on the invasion of hepatocellular carcinoma cell line HepG2 and the potential molecular mechanism. Methods By analyzing the sequencing results of liver cancer tissues and adjacent tissues in Gene Expression Omnibus (GEO) database, MTMR6 gene was screened out, and Spearman analysis was used to analyze the correlation of MTMR6 and pathway in the Cancer Genome Atlas (TCGA) database. Finally, the interaction between MTMR6 and signaling pathway proteins was analyzed with Genemania database. Then the expression of MTMR6 in human normal liver cell line LO-2 and hepatoma cell lines Huh-7 and HepG2 were measured and compared among the cell lines. Then HepG2 cells was selected as the study object. After MTMR6 gene was knocked down or over-expressed in HepG2 cells, Transwell assay was employed to observe invasion ability, and Western blotting was adopted to detect the expression of MTMR6, PI3K, p-PI3K, AKT, p-AKT, mTOR, p-mTOR MMP-2 and MMP-9. Results The expression of MTMR6 was significantly higher in the hepatocellular carcinoma tissues than the paracancer tissues, and it was in a positive linear correlation with PI3K/AKT/mTOR signaling pathway (P < 0.01), showing interaction with PI3K, AKT and mTOR. The expression level of MTMR6 was significantly higher in the HepG2 cells than the LO-2 and Huh-7 cells (P < 0.01). Over-expression of MTMR6 obviously enhanced invasion ability (P < 0.01), while its knockdown decreased the ability (P < 0.01) in HepG2 cells. Knockdown of MTMR6 gene also resulted in decreased phosphorylation of PI3K, AKT and mTOR, and expression levels of MMP-2 and MMP-9 (P < 0.01), while over-expression of MTMR6 promoted the phosphorylation of PI3K, AKT and mTOR, and up-regulated the expression of MMP-2 and MMP-9 (P < 0.01). In addition, LY294002 (a specific PI3K inhibitor) treatment could block the PI3K/AKT/mTOR pathway and down-regulate the expression of MMP-2 and MMP-9 (P < 0.01), but had no effect on MTMR6 expression. Conclusion MTMR6 may promote the invasion of hepatoma cells through activation of PI3K/AKT/mTOR signaling pathway.
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| first_indexed | 2024-03-08T03:06:50Z |
| format | Article |
| id | doaj.art-566777051b9d4ba7a3a6685870f9c4f7 |
| institution | Directory Open Access Journal |
| issn | 2097-0927 |
| language | zho |
| last_indexed | 2024-03-08T03:06:50Z |
| publishDate | 2024-02-01 |
| publisher | Editorial Office of Journal of Army Medical University |
| record_format | Article |
| series | 陆军军医大学学报 |
| spelling | doaj.art-566777051b9d4ba7a3a6685870f9c4f72024-02-13T08:37:26ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272024-02-0146324925610.16016/j.2097-0927.202304051Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathwayLIANG Xiao0CHEN Hongyu1PENG Xueqin2Department of General Medicine, University Town Hospital of Chongqing Medical University, Chongqing, 401331, ChinaDepartment of Gastroenterology, University Town Hospital of Chongqing Medical University, Chongqing, 401331, ChinaDepartment of General Medicine, University Town Hospital of Chongqing Medical University, Chongqing, 401331, ChinaObjective To explore the effect of myotubularin-related protein 6 (MTMR6) on the invasion of hepatocellular carcinoma cell line HepG2 and the potential molecular mechanism. Methods By analyzing the sequencing results of liver cancer tissues and adjacent tissues in Gene Expression Omnibus (GEO) database, MTMR6 gene was screened out, and Spearman analysis was used to analyze the correlation of MTMR6 and pathway in the Cancer Genome Atlas (TCGA) database. Finally, the interaction between MTMR6 and signaling pathway proteins was analyzed with Genemania database. Then the expression of MTMR6 in human normal liver cell line LO-2 and hepatoma cell lines Huh-7 and HepG2 were measured and compared among the cell lines. Then HepG2 cells was selected as the study object. After MTMR6 gene was knocked down or over-expressed in HepG2 cells, Transwell assay was employed to observe invasion ability, and Western blotting was adopted to detect the expression of MTMR6, PI3K, p-PI3K, AKT, p-AKT, mTOR, p-mTOR MMP-2 and MMP-9. Results The expression of MTMR6 was significantly higher in the hepatocellular carcinoma tissues than the paracancer tissues, and it was in a positive linear correlation with PI3K/AKT/mTOR signaling pathway (P < 0.01), showing interaction with PI3K, AKT and mTOR. The expression level of MTMR6 was significantly higher in the HepG2 cells than the LO-2 and Huh-7 cells (P < 0.01). Over-expression of MTMR6 obviously enhanced invasion ability (P < 0.01), while its knockdown decreased the ability (P < 0.01) in HepG2 cells. Knockdown of MTMR6 gene also resulted in decreased phosphorylation of PI3K, AKT and mTOR, and expression levels of MMP-2 and MMP-9 (P < 0.01), while over-expression of MTMR6 promoted the phosphorylation of PI3K, AKT and mTOR, and up-regulated the expression of MMP-2 and MMP-9 (P < 0.01). In addition, LY294002 (a specific PI3K inhibitor) treatment could block the PI3K/AKT/mTOR pathway and down-regulate the expression of MMP-2 and MMP-9 (P < 0.01), but had no effect on MTMR6 expression. Conclusion MTMR6 may promote the invasion of hepatoma cells through activation of PI3K/AKT/mTOR signaling pathway. http://aammt.tmmu.edu.cn/html/202304051.htmmtmr6pi3kaktmtorhepg2 cellsneoplasm invasion |
| spellingShingle | LIANG Xiao CHEN Hongyu PENG Xueqin Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway 陆军军医大学学报 mtmr6 pi3k akt mtor hepg2 cells neoplasm invasion |
| title | Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway |
| title_full | Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway |
| title_fullStr | Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway |
| title_full_unstemmed | Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway |
| title_short | Myotubularin-related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the PI3K/AKT/mTOR signaling pathway |
| title_sort | myotubularin related protein 6 promotes invasion of hepatocellular carcinoma cells by activating the pi3k akt mtor signaling pathway |
| topic | mtmr6 pi3k akt mtor hepg2 cells neoplasm invasion |
| url | http://aammt.tmmu.edu.cn/html/202304051.htm |
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