LncRNA SNHG11 Promotes Proliferation, Migration, Apoptosis, and Autophagy by Regulating hsa-miR-184/AGO2 in HCC

LncRNA SNHG11 Promotes Proliferation, Migration, Apoptosis, and Autophagy by Regulating hsa-miR-184/AGO2 in HCC
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DOI:
10.2147/ott.s237161
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发表时间:
2020-01-01
影响因子:
4
通讯作者:
Luo, Hongwu
Luo, Hongwu
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Wei;Huang, Feizhou;Luo, Hongwu

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背景:消化系统最常见的恶性肿瘤是肝细胞癌。然而,肝癌发生发展的机制和发病机制仍不清楚。LncRNA与肝癌的发生、发展密切相关。材料与方法:应用lncRNA芯片技术,筛选lncRNA在肝癌组织中的差异表达谱。RT-PCR检测SNHG 11、miR-184和GO2的表达。通过双荧光素酶测定和RIP揭示SNHG 11充当miRNA海绵的能力以及miR-184直接靶向mRNA的事实。Western blot检测细胞凋亡和自噬相关蛋白。结果:LncRNA微阵列和RT-PCR结果显示SNHG 11在肝癌组织中表达增强,在肝癌细胞中表达上调。SNHG 11与肝癌患者生存率低有关。此外,双荧光素酶测定和RIP结果显示SNHG 11充当miR-184的海绵,并且miR-184直接靶向AGO 2。Pearson相关分析显示SNHG 11与miR-184、miR-184与AGO 2呈负相关,SNHG 11与AGO 2呈正相关。结论:SNHG 11在肝癌组织中表达增高,且SNHG 11通过miR-184调控AGO 2,促进肝癌细胞增殖、迁移、凋亡和自噬。SNHG 11在肝癌诊断、治疗和预后中的作用可能为肝癌的诊断、治疗和预后提供新的生物标志物。
Background: The most common malignant tumor of the digestive system is HCC. However, the mechanism and pathogenesis of HCC occurrence and progress are still unknown. LncRNA is closely related to the occurrence and progress of HCC. It is important to investigate the effect and role of lncRNA in HCC.Materials and Methods: LncRNA microarray assay was used to screen the differential expression profile of lncRNA. SNHG11, miR-184 and GO2 expression was analyzed by RT-PCR. The ability of SNHG11 to serve as a sponge for miRNA and the fact that miR-184 directly targets mRNA were revealed by dual luciferase assay and RIP. Apoptosis and autophagy related proteins were detected by Western blot. Cell proliferation, invasion, migration, and apoptosis were detected by CCK-8 assay, wound healing assay, transwell assay, and flow cytometry.Results: LncRNA microarray assay and RT-PCR results revealed that the expression of SNHG11 was increased in HCC tumor tissues and also upregulated in HCC cells. SNHG11 had a connection with poor survival rate in HCC. In addition, dual luciferase assay and RIP results revealed that SNHG11 serves as a sponge for miR-184 and miR-184 directly targets AGO2. Pearson correlation analysis showed that SNHG11 with miR-184 and miR-184 with AGO2 were negative correlations, and SNHG11 with AGO2 was a positive correlation. Cell function assay and Western blot showed SNHG4/miR-184/AGO2 regulatory loop was critical for HCC cell proliferation, migration, apoptosis, and autophagy.Conclusion: Our study demonstrated that the expression of SNHG11 is higher in HCC; moreover, SNHG11 promotes proliferation, migration, apoptosis, and autophagy by regulating AGO2 via miR-184 in HCC. Our verification of the role of SNHG11 may provide a novel biomarker for the diagnosis, therapy, and prognosis of HCC.