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lncRNA OSER1-AS1 acts as a ceRNA to promote tumorigenesis in hepatocellular carcinoma by regulating miR-372-3p/Rab23 axis

机译:LNCRNA OSER1-AS1通过调节miR-372-3p / rab23轴来促进肝细胞癌中肿瘤内血管的Cerna

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Long non-coding RNAs (lncRNAs) are crucial regulators of tumorigenesis and progression in human cancer, including hepatocellular carcinoma (HCC). However, the role of most lncRNAs that are dysregulated in HCC remains to be elucidated. Here, we investigated the role of OSER1-AS1 in the progression of HCC. The results of database and qRT-PCR analysis demonstrated that OSER1-AS1 was highly expressed in HCC tissues and the high expression of OSER1-AS1 was closely associated with larger tumor size, advanced tumor stages, lower disease free survival and overall survival of HCC patients. OSER1-AS1 knockdown significantly inhibited the proliferation, invasion and migration of HCC cells, and induced the apoptosis. In addition, the dual luciferase reporter assay directly demonstrated that OSER1-AS1 functioned as a molecular sponge for miR-372-3p to promote Rab23 expression. Moreover, the results of immunohistochemistry and western blot analysis showed that Rab23 was highly expressed in HCC tissues, and the high expression of Rab23 was closely associated with the poor overall survival of HCC patients. Immunofluorescence assay also found the subcellular localization of Rab23 in HCC cells. Rab23 was obviously downregulated in cells that were transfected with miR-372-3p mimics. MiR-372-3p mimics significantly inhibited the proliferation and invasion of HCC cells). Rab23 restoration partially reversed miR-372-3p-induced tumor suppressive effects on HCC cells. In conclusion, we found that OSER1-AS1 acted as a ceRNA to sponge miR-372-3p, thereby positively regulating the Rab23 expression and ultimately acting as a tumor suppressor gene in HCC progression. (C) 2019 Elsevier Inc. All rights reserved.
机译:长期非编码RNA(LNCRNA)是人类癌症中肿瘤发生和进展的关键调节因子,包括肝细胞癌(HCC)。然而,大多数在HCC中具有失调的LNCRNA的作用仍有待阐明的待阐明。在这里,我们调查了OSER1-AS1在HCC进展中的作用。数据库和QRT-PCR分析的结果表明,OSER1-AS1在HCC组织中高度表达,并且OSER1-AS1的高表达与肿瘤大小,晚期肿瘤阶段,疾病免疫存活率降低和HCC患者的整体存活率密切相关。 OSER1-AS1敲低显着抑制HCC细胞的增殖,侵袭和迁移,并诱导细胞凋亡。此外,双荧光素酶报告结果直接证明OSER1-AS1用作MIR-372-3P的分子海绵,以促进RAB23表达。此外,免疫组织化学和蛋白质印迹分析结果表明,RAB23在HCC组织中高度表达,RAB23的高表达与HCC患者的差的整体存活密切相关。免疫荧光测定还发现HCC细胞中RAB23的亚细胞定位。在用miR-372-3p模拟中转染的细胞中明显下调Rab23。 miR-372-3p模仿显着抑制了HCC细胞的增殖和侵袭)。 RAB23恢复部分反转MIR-372-3P诱导的HCC细胞肿瘤抑制作用。总之,我们发现OSER1-AS1充当了海绵MIR-372-3P的CERNA,从而正弦调节RAB23表达并最终作用于HCC进展中的肿瘤抑制基因。 (c)2019 Elsevier Inc.保留所有权利。

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