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HOXA11-AS 通过与 EZH2 结合抑制 miR-124 的表达促进肝癌细胞的迁移和侵袭。

HOXA11-AS promotes the migration and invasion of hepatocellular carcinoma cells by inhibiting miR-124 expression by binding to EZH2.

机构信息

Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University, No.126, Xiantai Street, Changchun, 130033, Jilin, China.

Zhongyuan Union Clinical Laboratory Co., Ltd, Beijing, 100176, China.

出版信息

Hum Cell. 2019 Oct;32(4):504-514. doi: 10.1007/s13577-019-00269-x. Epub 2019 Sep 6.

Abstract

The objective of this study was to examine the function of the long non-coding RNA (lncRNA) HOXA11-AS in hepatocellular carcinoma (HCC). In total, samples from liver tumor and surrounding normal liver tissues were collected from 66 cases of HCC patients. Normal liver cell line HL-7702 and HCC cell lines HepG2, Hep3B, MHCC-97H and BEL7402 were used. Cells were transfected with different small interference RNAs or vectors. Then, transwell assay, qRT-PCR, CHIP, RIP and Western blot experiments were performed. We found that the HOXA11-AS expression level was higher in HCC samples than surrounding normal liver tissues. And the higher expression level of HOXA11-AS in HCC patients indicated a lower 5-year survival rate. Knockdown of HOXA11-AS in HepG2 and Hep3B cells caused impaired cell invasion and migration abilities. Otherwise, upregulation of HOXA11-AS in MHCC-97H and BEL7402 cells displayed higher invasion and migration capabilities. We also demonstrated that HOXA11-AS could inhibit miR-124 expression by binding to EZH2. Furthermore, overexpression of miR-124 or knockdown EZH2 expression could reverse the HOXA11-AS-induced migration and invasion effects in HCC cells. In summary, the high HOXA11-AS expression in HCC patients is associated with the poor outcome. HOXA11-AS could inhibit miR-124 expression by binding to EZH2 and thus promoted the migration and invasion of HCC cells.

摘要

本研究旨在探讨长链非编码 RNA(lncRNA)HOXA11-AS 在肝细胞癌(HCC)中的功能。共收集 66 例 HCC 患者的肝肿瘤及周围正常肝组织标本。使用正常肝细胞系 HL-7702 和 HCC 细胞系 HepG2、Hep3B、MHCC-97H 和 BEL7402。用不同的小干扰 RNA 或载体转染细胞。然后进行 Transwell 检测、qRT-PCR、CHIP、RIP 和 Western blot 实验。我们发现 HCC 样本中 HOXA11-AS 的表达水平高于周围正常肝组织。HOXA11-AS 在 HCC 患者中的高表达水平表明 5 年生存率较低。HepG2 和 Hep3B 细胞中 HOXA11-AS 的敲低导致细胞侵袭和迁移能力受损。相反,MHCC-97H 和 BEL7402 细胞中 HOXA11-AS 的上调显示出更高的侵袭和迁移能力。我们还证明 HOXA11-AS 可以通过与 EZH2 结合抑制 miR-124 的表达。此外,miR-124 的过表达或 EZH2 表达的敲低可以逆转 HOXA11-AS 诱导的 HCC 细胞迁移和侵袭作用。总之,HCC 患者中高 HOXA11-AS 表达与不良预后相关。HOXA11-AS 可以通过与 EZH2 结合抑制 miR-124 的表达,从而促进 HCC 细胞的迁移和侵袭。

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