FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients.
FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients.
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FOXA1 通过抑制男性患者中 PIK3R1 的表达来抑制肝细胞癌进展
DOI：
10.1186/s13046-017-0646-6
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发表时间：
2017-12-06
期刊：
影响因子：
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通讯作者：
Luo R
中科院分区：
文献类型：
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作者：
He S;Zhang J;Zhang W;Chen F;Luo R
叉头盒A1（FOXA1）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，我们通过对 HepG2 和 Hep3B 细胞系进行基因功能增益和缺失分析，并将结果与临床 HCC 样本的结果进行比较，研究了 FOXA1 在 HCC 发展中的作用。编码蛋白质 PI3Kp85 (p85) 的磷酸肌醇 3-激酶调节亚基 1 (PIK3R1) 被确定为 FOXA1 靶基因。机制和功能分析表明，FOXA1 通过直接抑制 PIK3R1 转录来抑制 PI3K/Akt 信号传导，从而抑制肝细胞癌细胞的活力和运动。此外，在男性 HCC 患者的临床样本中，肿瘤组织中的 FOXA1 表达要低得多，而 PI3Kp85 水平要远高于非肿瘤组织。 PI3Kp85 升高是 HCC 的不利因素。作为肿瘤抑制因子，FOXA1直接靶向PIK3R1抑制PI3K/Akt信号通路，从而对男性患者HCC的增殖、迁移和侵袭发挥负调节作用。本文的在线版本 (10.1186/s13046-017-0646-6) 包含补充材料，可供授权用户使用。
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. The online version of this article (10.1186/s13046-017-0646-6) contains supplementary material, which is available to authorized users.