FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients
Abstract Background Forkhead box A1 (FOXA1) expression is associated with various types of tumors; however, the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure. Methods Here, we investigated the role of FOXA1 in the development of HCC b...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-12-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-017-0646-6 |
| _version_ | 1818126338591031296 |
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| author | Shujiao He Junyi Zhang Wan Zhang Fengsheng Chen Rongcheng Luo |
| author_facet | Shujiao He Junyi Zhang Wan Zhang Fengsheng Chen Rongcheng Luo |
| author_sort | Shujiao He |
| collection | DOAJ |
| description | Abstract Background Forkhead box A1 (FOXA1) expression is associated with various types of tumors; however, the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure. Methods Here, we investigated the role of FOXA1 in the development of HCC by applying gene function gain and loss analysis to HepG2 and Hep3B cell lines, and comparing outcomes with those of clinical HCC samples. Results Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), which encodes protein PI3Kp85 (p85), was identified as a FOXA1 target gene. Analyses of the mechanism and function revealed that FOXA1 suppresses hepatocellular carcinoma cell viability and motility by inhibiting PI3K/Akt signaling through direct inhibition of PIK3R1 transcription. Moreover, in clinical samples from male HCC patients, FOXA1 expression was much lower, whereas PI3Kp85 levels were much higher in tumor than in non-tumor tissues. Elevated PI3Kp85 is an unfavorable factor in HCC. Conclusions As a tumor suppressor, FOXA1 targets PIK3R1 directly to inhibit PI3K/Akt signaling pathway, thus exerting a negative regulatory effect on proliferation, migration, and invasion of HCC in male patients. |
| first_indexed | 2024-12-11T06:59:53Z |
| format | Article |
| id | doaj.art-2e7eed3a6373493e8e7b50fe70029c60 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-11T06:59:53Z |
| publishDate | 2017-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-2e7eed3a6373493e8e7b50fe70029c602022-12-22T01:16:39ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662017-12-0136111010.1186/s13046-017-0646-6FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patientsShujiao He0Junyi Zhang1Wan Zhang2Fengsheng Chen3Rongcheng Luo4Cancer Center, Southern Medical UniversityCancer Center, Southern Medical UniversityCancer Center, Southern Medical UniversityCancer Center, Southern Medical UniversityCancer Center, Southern Medical UniversityAbstract Background Forkhead box A1 (FOXA1) expression is associated with various types of tumors; however, the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure. Methods Here, we investigated the role of FOXA1 in the development of HCC by applying gene function gain and loss analysis to HepG2 and Hep3B cell lines, and comparing outcomes with those of clinical HCC samples. Results Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), which encodes protein PI3Kp85 (p85), was identified as a FOXA1 target gene. Analyses of the mechanism and function revealed that FOXA1 suppresses hepatocellular carcinoma cell viability and motility by inhibiting PI3K/Akt signaling through direct inhibition of PIK3R1 transcription. Moreover, in clinical samples from male HCC patients, FOXA1 expression was much lower, whereas PI3Kp85 levels were much higher in tumor than in non-tumor tissues. Elevated PI3Kp85 is an unfavorable factor in HCC. Conclusions As a tumor suppressor, FOXA1 targets PIK3R1 directly to inhibit PI3K/Akt signaling pathway, thus exerting a negative regulatory effect on proliferation, migration, and invasion of HCC in male patients.http://link.springer.com/article/10.1186/s13046-017-0646-6FOXA1Hepatocellular carcinomaPIK3R1/PI3Kp85PI3K/Akt |
| spellingShingle | Shujiao He Junyi Zhang Wan Zhang Fengsheng Chen Rongcheng Luo FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients Journal of Experimental & Clinical Cancer Research FOXA1 Hepatocellular carcinoma PIK3R1/PI3Kp85 PI3K/Akt |
| title | FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients |
| title_full | FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients |
| title_fullStr | FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients |
| title_full_unstemmed | FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients |
| title_short | FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients |
| title_sort | foxa1 inhibits hepatocellular carcinoma progression by suppressing pik3r1 expression in male patients |
| topic | FOXA1 Hepatocellular carcinoma PIK3R1/PI3Kp85 PI3K/Akt |
| url | http://link.springer.com/article/10.1186/s13046-017-0646-6 |
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