Abstract
BackgroundForkhead 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.MethodsHere, 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.ResultsPhosphoinositide-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.ConclusionsAs 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.
Highlights
Forkhead box A1 (FOXA1) expression is associated with various types of tumors; the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure
Lentivirus infection HepG2 and Hep3B cells were infected with FOXA1overexpressing lentivirus (GeneChem, Shanghai, China), after which FOXA1 expression was confirmed by quantitative reverse transcription polymerase chain reaction and western blotting
FOXA1 suppresses viability and motility of liver carcinoma cells To investigate the role of FOXA1 in HCC development, we first investigated the effect of FOXA1 on cell viability and motility in HepG2 and Hep3B cells
Summary
Forkhead box A1 (FOXA1) expression is associated with various types of tumors; the function and underlying mechanism of FOXA1 in the development of hepatocellular carcinoma (HCC) remains obscure. Hepatocellular carcinoma (HCC) is one of the deadliest cancers worldwide [1, 2]. As HCC is a highly heterogeneous disease, several genes and proteins are known to contribute to its tumorigenesis and progression [3]. Forkhead box A1 (FOXA1), called HNF3A [4], is a member of the forkhead family of DNA-binding proteins, which are known for their role in regulating metabolism. FOXA proteins include three members, FOXA1, FOXA2, and FOXA3, each encoded by an individual gene [5]. Increasing evidence indicates that FOXA factors are involved in the development and progression of several tumors [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Journal of Experimental & Clinical Cancer Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
