Cancer Center, Southern Medical University, Guangzhou, Guangdong, 510315, China.
Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510315, China.
J Exp Clin Cancer Res. 2017 Dec 6;36(1):175. doi: 10.1186/s13046-017-0646-6.
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.
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.
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.
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.
叉头框蛋白 A1（FOXA1）的表达与多种类型的肿瘤相关；然而，FOXA1 在肝细胞癌（HCC）发展中的功能和潜在机制仍不清楚。
在这里，我们通过在 HepG2 和 Hep3B 细胞系中应用基因功能获得和缺失分析，研究了 FOXA1 在 HCC 发展中的作用，并将结果与临床 HCC 样本进行了比较。
鉴定出磷酸肌醇-3-激酶调节亚基 1（PIK3R1）是 FOXA1 的靶基因，其编码蛋白为 PI3Kp85（p85）。通过直接抑制 PIK3R1 转录，FOXA1 抑制 PI3K/Akt 信号通路从而抑制肝癌细胞活力和迁移的机制和功能分析表明。此外，在男性 HCC 患者的临床样本中，FOXA1 的表达水平明显较低，而肿瘤组织中 PI3Kp85 的水平明显高于非肿瘤组织。PI3Kp85 升高是 HCC 的不利因素。
作为一种肿瘤抑制因子，FOXA1 直接靶向 PIK3R1 以抑制 PI3K/Akt 信号通路，从而对男性 HCC 患者的增殖、迁移和侵袭产生负向调节作用。
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