转移
癌症研究
细胞生长
碘化丙啶
PI3K/AKT/mTOR通路
蛋白激酶B
细胞凋亡
细胞迁移
肝细胞癌
生物
上皮-间质转换
细胞
信号转导
医学
癌症
内科学
程序性细胞死亡
细胞生物学
生物化学
遗传学
作者
Zhenjie Li,Jinping Zhang,Dongying Li,Hua Yang,Shi Hai
摘要
Due to high invasion and metastasis, hepatocellular carcinoma (HCC) is known as one of the most fatal carcinomas. We aim to further investigate regulatory mechanisms of invasion and metastasis to elucidate HCC pathogenesis and develop novel medications.Patient specimens were collected for assessing gene expression and correlation between gene expressions. The expression of Ki67 and E-cadherin in subcutaneous xenograft tumor were examined by immunohistochemistry staining. The expression of activating transcription factor 2 (ATF2), miR-548p and TUFT1 were determined using Real-time quantitative reverse transcription polymerase chain reaction. Epithelial-mesenchymal transition and PI3K/AKT signaling-associated markers were examined with western blot. The proliferation, migration and invasion were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, colony formation and transwell assays, respectively. Cell apoptosis was assessed via Annexin V and propidium iodide staining. Gene interaction was confirmed using chromatin immunoprecipitation and luciferase activity assays. Subcutaneous and intravenous xenograft mouse models were established for analyzing HCC growth and metastasis in vivo.ATF2 was up-regulated in HCC patients and cells. ATF2 promoted HCC cell proliferation, migration and invasion and inhibited cell apoptosis through directly targeting miR-548p and controlling its expression. miR-548p suppressed HCC cell proliferation, migration and invasion and enhanced cell apoptosis. miR-548p directly bound to the 3'UTR of TUFT1 to restrain its expression and subsequently suppress the PI3K/AKT signaling. ATF2 knock-down significantly suppressed the growth and metastasis of HCC.ATF2 accelerates HCC progression by promoting cell proliferation, migration, invasion and metastasis, which is dependent on regulating the miR-548p/TUFT1 axis.
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