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LINC01296 通过调节 microRNA-760 的表达促进肝癌的增殖和侵袭,并预测其预后不良。

LINC01296 promotes the proliferation and invasion by regulating microRNA-760 expression and predicts poor prognosis of hepatocellular carcinoma.

机构信息

Department of Spleen, Stomach and Liver Diseases, Guangxi International Zhuang Medical Hospital, Nanning, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):9848-9856. doi: 10.26355/eurrev_201911_19548.

Abstract

OBJECTIVE

The aim of this study was to investigate the role of LINC01296 in the progression of liver cancer (LCa) and to explore its possible molecular mechanisms.

PATIENTS AND METHODS

TCGA database was used for information mining to verify the expression of LINC01296 in liver tumor tissues and normal tissues. The levels of LINC01296 in 40 pairs of LCa and adjacent tissues, as well as normal liver cell lines and liver cancer cell lines, were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The Chi-square test was performed to analyze the clinical characteristics of tumor samples and LINC01296 expression. Meanwhile, the Chi-square test was used to explore the relationship between different clinical indicators and the expression of LINC01296. The liver cancer cell lines were screened and transfected with siRNA-LINC01296 and microRNA-760 inhibitor, as well as corresponding negative controls, respectively. Cell counting kit-8 (CCK-8) and Transwell assays were used to determine the effects of LINC01296 on the proliferative and invasive capacities of cells. Furthermore, the regulatory association between LINC01296 and microRNA-760 was verified by the Dual-Luciferase reporter assay.

RESULTS

LINC01296 expression was remarkably higher in LCa tissues than that of normal liver tissues. Meanwhile, LINC01296 expression was associated with poor prognosis of LCa. Patients with high LINC01296 expression were more likely to have lymph node metastasis. In vitro experiments showed that the knockdown of LINC01296 significantly inhibited the proliferation and migration of HCC cells. Meanwhile, microRNA-760 was remarkably lowly expressed in LCa tissues and cells. Subsequent experiments indicated that LINC01296 was regulated by miR760 in LCa tissues, and high expression of linc0129 could limit microRNA-760 expression. Furthermore, the inhibition of microRNA-760 in HCC cells reversed the effect of LINC01296 knockdown on cell proliferation and invasion.

CONCLUSIONS

LINC01296 could promote the proliferative ability and invasiveness of hepatoma cells by inhibiting the expression of microRNA-760. Moreover, its expression was closely related to lymph node metastasis and poor prognosis of LCa.

摘要

目的

本研究旨在探讨 LINC01296 在肝癌(LCa)进展中的作用,并探讨其可能的分子机制。

方法

利用 TCGA 数据库进行信息挖掘,验证 LINC01296 在肝肿瘤组织和正常组织中的表达。采用实时定量聚合酶链反应(qRT-PCR)检测 40 对 LCa 及相邻组织、正常肝细胞系和肝癌细胞系中 LINC01296 的水平。采用卡方检验分析肿瘤样本的临床特征与 LINC01296 表达的关系。同时,采用卡方检验探讨不同临床指标与 LINC01296 表达的关系。筛选肝癌细胞系,分别用 siRNA-LINC01296 和 microRNA-760 抑制剂及其相应的阴性对照转染,采用细胞计数试剂盒-8(CCK-8)和 Transwell 实验检测 LINC01296 对细胞增殖和侵袭能力的影响。此外,采用双荧光素酶报告基因实验验证 LINC01296 与 microRNA-760 的调控关系。

结果

LINC01296 在 LCa 组织中的表达明显高于正常肝组织。同时,LINC01296 的表达与 LCa 的预后不良有关。LINC01296 高表达的患者更有可能发生淋巴结转移。体外实验表明,LINC01296 的敲低显著抑制 HCC 细胞的增殖和迁移。同时,microRNA-760 在 LCa 组织和细胞中表达明显降低。后续实验表明,LINC01296 在 LCa 组织中受 miR760 调控,高表达的 linc0129 可限制 microRNA-760 的表达。此外,在 HCC 细胞中抑制 microRNA-760 可逆转 LINC01296 敲低对细胞增殖和侵袭的影响。

结论

LINC01296 可通过抑制 microRNA-760 的表达促进肝癌细胞的增殖能力和侵袭性。此外,其表达与 LCa 的淋巴结转移和不良预后密切相关。

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