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NEAT1 对于肝癌干细胞标志物 CD44 的表达是必需的。

NEAT1 is Required for the Expression of the Liver Cancer Stem Cell Marker CD44.

机构信息

Division of Molecular and Genetic Medicine, Graduate School of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan.

Division of Surgical Oncology, Department of Surgery, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan.

出版信息

Int J Mol Sci. 2020 Mar 11;21(6):1927. doi: 10.3390/ijms21061927.

DOI:10.3390/ijms21061927
PMID:32168951
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7139689/
Abstract

CD44, a cancer stem cell (CSC) marker, is required for maintaining CSC properties in hepatocellular carcinoma (HCC). Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), is an oncogenic driver in HCC. In the present study, we investigated the significance of the gene in association with CD44 expression in liver CSCs of human HCC cell lines. The CSC properties were evaluated by spheroid culture, CSC marker expression, and sensitivity to anti-cancer drugs. The expression of both NEAT1 variant 1 (NEAT1v1) and variant 2 (NEAT1v2) as well as CD44 was significantly increased in the spheroid culture, compared with that in monolayer culture. Overexpression of Neat1v1, but not Neat1v2, enhanced the CSC properties, while knockout of the NEAT1 gene suppressed them. CD44 expression was increased by the overexpression of Neat1v1 and abrogated by NEAT1 knockout. The overexpression of NEAT1v1 restored the CSC properties and CD44 expression in NEAT1-knockout cells. NEAT1v1 expression in HCC tissues was correlated with poor prognosis and CD44 expression. These results suggest that NEAT1v1 is required for CD44 expression. To our surprise, NEAT1v1 also restored the CSC properties even in CD44-deficient cells, suggesting that NEAT1v1 maintains the properties of CSCs in a CD44-independent manner.

摘要

CD44 是癌症干细胞 (CSC) 的标志物,对于维持肝癌 (HCC) 中的 CSC 特性是必需的。核富集丰富转录本 1 (NEAT1) 是一种长链非编码 RNA (lncRNA),是 HCC 中的致癌驱动因子。在本研究中,我们研究了基因在与人 HCC 细胞系的肝 CSCs 中与 CD44 表达相关联的意义。通过球体培养、CSC 标志物表达和对抗癌药物的敏感性来评估 CSC 特性。与单层培养相比,球体培养中明显增加了 NEAT1 变体 1 (NEAT1v1) 和变体 2 (NEAT1v2) 以及 CD44 的表达。Neat1v1 的过表达增强了 CSC 特性,而 NEAT1 基因的敲除则抑制了它们,而 Neat1v2 的过表达则没有。Neat1v1 的过表达增加了 CD44 的表达,并通过 NEAT1 敲除消除了这种表达。NEAT1v1 的过表达在 NEAT1 敲除细胞中恢复了 CSC 特性和 CD44 表达。HCC 组织中 NEAT1v1 的表达与预后不良和 CD44 表达相关。这些结果表明,NEAT1v1 是 CD44 表达所必需的。令我们惊讶的是,即使在 CD44 缺陷细胞中,NEAT1v1 也能恢复 CSC 特性,这表明 NEAT1v1 以 CD44 独立的方式维持 CSCs 的特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a73/7139689/e694fba01ae1/ijms-21-01927-g007.jpg
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