Long noncoding RNA LINC00324 exerts protumorigenic effects on liver cancer stem cells by upregulating fas ligand via PU box binding protein
Long noncoding RNA LINC00324 exerts protumorigenic effects on liver cancer stem cells by upregulating fas ligand via PU box binding protein
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DOI：
10.1096/fj.201902705rr
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发表时间：
2020-03-03
期刊：
影响因子：
4.8
通讯作者：
Zhou, Fan
中科院分区：
文献类型：
--
作者：
Gao, Jun;Dai, Chao;Zhou, Fan
肝细胞癌（HCC）是癌症死亡的主要原因，但其发展的分子机制尚未得到很好的表征。长链非编码rna （lncRNAs）作为癌基因或肿瘤抑制基因参与了广泛的生物学过程。本研究旨在阐明LINC00324通过其与Fas配体（FasL）的相互作用在HCC中的作用。最初，采用基于微阵列的HCC基因表达谱来鉴定差异表达基因。接下来，采用RT-qPCR检测LINC00324在HCC组织和肝癌干细胞（LCSC）中的表达。然后，利用RIP、ChIP和双荧光素酶报告基因检测方法鉴定LINC00324、PU box binding protein （PU.1）和FasL之间的相互作用。通过功能获得和功能丧失实验检测LINC00324对转染细胞的活力、增殖、迁移、侵袭、凋亡以及肿瘤发生的影响。LINC00324和FasL在HCC中高表达。LINC00324通过与PU.1的相互作用调控FasL的表达。沉默LINC00324或FasL抑制干细胞相关基因的表达、细胞活力、增殖、迁移、侵袭、自我更新和肿瘤发生，但增强细胞凋亡。综上所述，LINC00324通过募集PU.1来促进FasL的表达，最终维持LCSCs的生物学特性，因此，LINC00324是一种有前景的HCC治疗候选药物。
Hepatocellular carcinoma (HCC) represents a major cause of cancer death, but the molecular mechanism for its development has not yet been well characterized. Long noncoding RNAs (lncRNAs) are involved in a wide range of biological processes via their roles as oncogenes or tumor suppressor genes. The present study aimed to elucidate the role of LINC00324 in HCC through its interaction with Fas ligand (FasL). Initially, microarray-based gene expression profiling of HCC was employed to identify differentially expressed genes. Next, the expression of LINC00324 in HCC tissues and liver cancer stem cell (LCSC) lines was examined using RT-qPCR. Then, the interaction among LINC00324, PU box binding protein (PU.1) and FasL was identified with RIP, ChIP and dual-luciferase reporter gene assays. The effect of LINC00324 on viability, proliferation, migration, invasion, and apoptosis as well as the tumorigenesis of transfected cells was examined with gain- and loss-of-function experiments. LINC00324 and FasL were highly expressed in HCC. LINC00324 regulated FasL expression via interaction with PU.1. Silencing of LINC00324 or FasL suppressed expression of stemness-related genes, cell viability, proliferation, migration, invasion, self-renewal, and tumorigenesis, but enhanced cell apoptosis. Taken together, LINC00324 promotes the expression of FasL through the recruitment of PU.1, which ultimately maintains the biological properties of LCSCs, thus, highlighting LINC00324 as a promising therapeutic candidate for HCC.