LncRNA FOXD3-AS1 Mediates AKT Pathway to Promote Growth and Invasion in Hepatocellular Carcinoma Through Regulating RICTOR
LncRNA FOXD3-AS1 Mediates AKT Pathway to Promote Growth and Invasion in Hepatocellular Carcinoma Through Regulating RICTOR
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DOI：
10.1089/cbr.2019.3335
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发表时间：
2020-05-01
影响因子：
3.4
通讯作者：
Zhang, Rui
中科院分区：
文献类型：
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作者：
Liu, Chao;Zhang, Meng;Zhang, Rui
背景：肝细胞癌（HCC）具有较高的发病率和死亡率，但目前的治疗方法不能有效改善患者的预后。 FOXD3-AS1 是一种新发现的长非编码 RNA，在多种癌症中失调，并充当致癌或肿瘤抑制因子。然而，FOXD3-AS1在HCC中的功能尚未见报道。 材料与方法：应用实时定量聚合酶链反应评估FOXD3-AS1在HCC组织和细胞系中的表达。利用 miRDB 和 TargetScan 网站来预测 FOXD3-AS1 作为竞争性内源 RNA 的相互作用网络。通过荧光素酶报告基因测定和 RNA 结合蛋白免疫沉淀 (RIP) 测定证实了相互作用。采用细胞计数试剂盒（CCK）-8、BrdU细胞增殖实验、Transwell侵袭实验、伤口愈合实验等检测FOXD3-AS1对HCC细胞（Huh6）的影响。结果：FOXD3-AS1在HCC中过表达，FOXD3-AS1高水平的HCC患者预后较差。此外，FOXD3-AS1敲低显着抑制Huh6细胞的增殖、迁移和侵袭。此外，FOXD3-AS1充当miR-335的海绵，而RICTOR是miR-335的直接靶基因。此外，FOXD3-AS1 可以通过海绵 miR-335 来增强 RICTOR 的水平。此外，FOXD3-AS1的敲低可以与miR-335竞争性结合，抑制RICTOR的表达，从而通过AKT信号通路失活来抑制Huh6细胞的生长。结论：FOXD3-AS1在HCC的发生和发展中至关重要。 FOXD3-AS1、miR-335和RICTOR之间的相互作用为理解HCC的分子机制提供了新的见解，FOXD3-AS1、miR-335和RICTOR可被视为HCC治疗的潜在靶点。
Background: Hepatocellular carcinoma (HCC) has high morbidity and mortality, but current therapeutic methods cannot effectively improve patient's prognosis. FOXD3-AS1, a new identified long noncoding RNA, is dysregulated in several cancers and functions as a carcinogenic or tumor-suppressor factor. However, the function of FOXD3-AS1 in HCC has not been reported.Materials and Methods: Quantitative real time-polymerase chain reaction was applied to evaluate the expression of FOXD3-AS1 in HCC tissues and cell lines. miRDB and TargetScan websites were utilized to predict the interaction network of FOXD3-AS1 as a competing endogenous RNA. The interaction was confirmed by luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. The effect of FOXD3-AS1 on HCC cells (Huh6) were measured by cell counting kit (CCK)-8, BrdU cell proliferation assay, Transwell invasion assay, and wound healing assay.Results: FOXD3-AS1 was overexpressed in HCC, and HCC patients with the high level of FOXD3-AS1 had a poor prognosis. In addition, FOXD3-AS1 knockdown considerably inhibited the proliferation, migration, and invasion of Huh6 cells. Besides, FOXD3-AS1 functioned as a sponge of miR-335, and RICTOR was a direct target gene of miR-335. Furthermore, FOXD3-AS1 could enhance the level of RICTOR through sponging miR-335. Moreover, the knockdown of FOXD3-AS1 could competitively bind with miR-335 to suppress RICTOR expression, thereby inhibiting the growth of Huh6 cells through the deactivation of AKT signaling pathway.Conclusions: FOXD3-AS1 is crucial for the tumorigenesis and progression of HCC. The interaction among FOXD3-AS1, miR-335, and RICTOR provides a novel insight for understanding the molecular mechanism of HCC, and FOXD3-AS1, miR-335, and RICTOR can be regarded as the potential targets for HCC treatment.