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Evaluation of LncRNA ANRIL Potential in Hepatic Cancer Progression.
Journal of Environmental Pathology, Toxicology and Oncology ( IF 2.4 ) Pub Date : 2019-11-05 , DOI: 10.1615/jenvironpatholtoxicoloncol.2019028282
Yongjian Ji 1 , Hao Sun 2 , Haiqing Liang 2 , Yong Wang 2 , Meili Lu 2 , Zhaoyang Guo 1 , Zhuozhen Lv 1 , Wanhua Ren 1
Affiliation  

BACKGROUND/AIMS LncRNAs are significant regulators in multiple cancers including hepatocellular carcinoma (HCC). Recently, lncRNA ANRIL has been reported to be elevated during multiple cancer types, exhibiting oncogenic roles. However, the exact biological mechanism of ANRIL is still poorly understood in HCC. METHODS Quantitative real-time polymerase chain reaction (qRT-PCR) assays were utilized to detect expressions of ANRIL, miR-384, and STAT3. CCK8 and EDU assays were employed to evaluate HCC cell proliferation. A flow cytometry assay was used to detect the HCC cell cycle and cell apoptosis. The scratch migration and Transwell invasion assays were performed to test cell migration and invasion, respectively. RIP and RNA pull-down assays were carried out to confirm the correlation between ANRIL and miR-384. The dual-luciferase reporter assay was used to prove the association between miR-384 and STAT3. Western blotting analysis was performed to examine protein levels of STAT3. IHC and HE staining were employed to detect Ki-67 and histopathology. RESULTS ANRIL expression was upregulated in HCC cells, including SMCC7721, HepG2, MHCC-97H, SNU449 and HUH-7 cells, in comparison to the normal human liver cells LO2. Knockdown of ANRIL suppressed HCC cell proliferation and induced cell cycle arrest and apoptosis. HCC cell migration and invasion capacity were inhibited by inhibition of ANRIL. Bioinformatics analyses revealed that ANRIL could interact with miR-384. miR-384 was significantly decreased in HCC cells, and overexpression of miR-384 repressed HCC progression. STAT3 was predicted as a target of miR-384, and miR-384 can modulate STAT3 levels negatively in vitro. ANRIL can suppress HCC development through regulating miR-384 and STAT3 in vivo. CONCLUSION ANRIL is involved in HCC progression by direct targeting of miR-384 and STAT3. Also, ANRIL could act as a potential candidate for HCC diagnosis, prognosis, and therapy.

中文翻译:

肝癌进展中LncRNA ANRIL潜力的评估。

背景/目的LncRNA在包括肝细胞癌(HCC)在内的多种癌症中是重要的调节因子。最近,据报道lncRNA ANRIL在多种癌症类型中升高,表现出致癌作用。然而,在肝癌中对ANRIL的确切生物学机制仍知之甚少。方法采用定量实时聚合酶链反应(qRT-PCR)方法检测ANRIL,miR-384和STAT3的表达。CCK8和EDU测定法用于评估HCC细胞增殖。流式细胞术用于检测HCC细胞周期和细胞凋亡。进行了划痕迁移和Transwell侵袭测定,以分别测试细胞迁移和侵袭。进行了RIP和RNA下拉测定,以确认ANRIL和miR-384之间的相关性。使用双重荧光素酶报告基因试验来证明miR-384与STAT3之间的关联。进行蛋白质印迹分析以检查STAT3的蛋白水平。IHC和HE染色用于检测Ki-67和组织病理学。结果与正常人肝细胞LO2相比,ANRIL表达在包括SMCC7721,HepG2,MHCC-97H,SNU449和HUH-7细胞在内的HCC细胞中表达上调。降低ANRIL抑制HCC细胞增殖并诱导细胞周期停滞和凋亡。抑制ANRIL抑制HCC细胞迁移和侵袭能力。生物信息学分析表明,ANRIL可以与miR-384相互作用。miR-384在HCC细胞中显着降低,而miR-384的过表达抑制HCC进程。STAT3被预测为miR-384的靶标,而miR-384可以在体外负面调节STAT3水平。ANRIL可通过在体内调节miR-384和STAT3抑制HCC的发展。结论ANRIL通过直接靶向miR-384和STAT3参与HCC进展。而且,ANRIL可以作为HCC诊断,预后和治疗的潜在候选者。
更新日期:2019-11-01
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