miR‐190 promotes HCC proliferation and metastasis by targeting PHLPP1
miR‐190 promotes HCC proliferation and metastasis by targeting PHLPP1
复制标题
DOI：
10.1016/j.yexcr.2018.08.008
复制
发表时间：
2018-10
影响因子：
3.7
通讯作者：
Yuzhen Xiong;Shang-Ru Wu;Hua-Jun Yu;Jun Wu;Yajun Wang;Huimin Li;Hui-Yao Huang;Haitao Zhang
中科院分区：
文献类型：
--
作者：
Yuzhen Xiong;Shang-Ru Wu;Hua-Jun Yu;Jun Wu;Yajun Wang;Huimin Li;Hui-Yao Huang;Haitao Zhang
miRNA 调节基因表达，使临床医生能够区分癌症中的良性和恶性组织。 PH 结构域富含亮氨酸重复序列的蛋白磷酸酶 1 (PHLPP1) 已知是一种肿瘤抑制因子。利用慢病毒过表达系统稳定表达miR-190，抑制PHLPP1表达，从而增强肝细胞癌（HCC）增殖和转移。结果显示，稳定的 miR-190 表达增加了 EMT 相关蛋白（Snail 和 TCF8/ZEB1）的表达以及 Akt Ser473 的磷酸化以及具有血小板反应蛋白基序 1 (ADAMTS1) 的解整合素和金属蛋白酶的表达。然而，恢复PHLPP1表达抵消了miR-190对HCC增殖、迁移和侵袭的影响。动物实验结果表明，miR-190提高了HepG2细胞的肿瘤形成和肺转移能力。稳定的 miR-190 过表达导致 PHLPP1 蛋白表达下调。 miR-190 有潜力作为 HCC 治疗和诊断的靶点。
miRNAs regulate gene expression and enable clinicians to distinguish between benign and malignant tissues in cancers. PH domain leucine-rich repeat-containing protein phosphatase 1 (PHLPP1) is known to be a tumour suppressor. A lentiviral overexpression system was used to stably express miR-190, leading to the enhancement of hepatocellular carcinoma (HCC) proliferation and metastasis as a result of inhibited PHLPP1 expression. The results showed that stable miR-190 expression increased the expression of EMT-related proteins (Snail and TCF8/ZEB1) as well as the phosphorylation of Akt at Ser473 and the expression of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). However, restoring PHLPP1 expression counteracted the effects of miR-190 on HCC proliferation, migration and invasion. The results of the animal experiments showed that miR-190 improved the HepG2 cell tumour formation and lung metastasis ability. Stable miR-190 overexpression leads to the downregulation of PHLPP1 protein expression. miR-190 has potential as a target in the treatment and diagnosis of HCC.