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特异性蛋白（Sp）转录因子和二甲双胍调节长链非编码RNA HULC的表达。

Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC.

作者信息

Gandhy Shruti U, Imanirad Parisa, Jin Un-Ho, Nair Vijayalekshmi, Hedrick Eric, Cheng Yating, Corton J Christopher, Kim KyoungHyun, Safe Stephen

机构信息

Institute of Biosciences and Technology, Texas A&M Health Sciences Center, Houston, TX, USA.

Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.

出版信息

Oncotarget. 2015 Sep 22;6(28):26359-72. doi: 10.18632/oncotarget.4560.

DOI:10.18632/oncotarget.4560
PMID:26317792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4694907/
Abstract

Specificity protein 1 (Sp1) transcription factor (TF) regulates expression of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) cells. RNA interference (RNAi) studies showed that among several lncRNAs expressed in HepG2, SNU-449 and SK-Hep-1 cells, highly upregulated in liver cancer (HULC) was regulated not only by Sp1 but also Sp3 and Sp4 in the three cell lines. Knockdown of Sp transcription factors and HULC by RNAi showed that they play important roles in HCC cell proliferation, survival and migration. The relative contribution of Sp1, Sp3, Sp4 and HULC on these responses in HepG2, SNU-449 and SK-Hep-1 cells were cell context- and response-dependent. In the poorly differentiated SK-Hep-1 cells, knockdown of Sp1 or HULC resulted in genomic and morphological changes, indicating that Sp1 and Sp1-regulated HULC are important for maintaining the mesenchymal phenotype in this cell line. Genomic analysis showed an inverse correlation between expression of genes after knockdown of HULC and expression of those genes in liver tumors from patients. The antidiabetic drug metformin down-regulates Sp proteins in pancreatic cancer, and similar results including decreased HULC expression were observed in HepG2, SNU-449 and SK-Hep-1 cells treated with metformin, indicating that metformin and other antineoplastic agents that target Sp proteins may have clinical applications for HCC chemotherapy.

摘要

特异性蛋白1（Sp1）转录因子（TF）调节肝癌（HCC）细胞中长链非编码RNA（lncRNA）的表达。RNA干扰（RNAi）研究表明，在HepG2、SNU-449和SK-Hep-1细胞中表达的几种lncRNA中，肝癌中高度上调的长链非编码RNA（HULC）不仅受Sp1调节，还受这三种细胞系中的Sp3和Sp4调节。通过RNAi敲低Sp转录因子和HULC表明，它们在HCC细胞增殖、存活和迁移中发挥重要作用。Sp1、Sp3、Sp4和HULC对HepG2、SNU-449和SK-Hep-1细胞中这些反应的相对贡献取决于细胞背景和反应。在低分化的SK-Hep-1细胞中，敲低Sp1或HULC会导致基因组和形态学变化，表明Sp1和Sp1调节的HULC对维持该细胞系的间充质表型很重要。基因组分析显示，敲低HULC后基因的表达与患者肝肿瘤中这些基因的表达呈负相关。抗糖尿病药物二甲双胍可下调胰腺癌中的Sp蛋白，在用二甲双胍处理的HepG2、SNU-449和SK-Hep-1细胞中也观察到了类似结果，包括HULC表达降低，这表明二甲双胍和其他靶向Sp蛋白的抗肿瘤药物可能在HCC化疗中有临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/10b480f8a3b3/oncotarget-06-26359-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/1a385589bb92/oncotarget-06-26359-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/5668b212e350/oncotarget-06-26359-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/10b480f8a3b3/oncotarget-06-26359-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/1a385589bb92/oncotarget-06-26359-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/0a0b857fa2c4/oncotarget-06-26359-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/ebd005025f4f/oncotarget-06-26359-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/db0075fdf7f4/oncotarget-06-26359-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/1a5892e7605d/oncotarget-06-26359-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/5668b212e350/oncotarget-06-26359-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4410/4694907/10b480f8a3b3/oncotarget-06-26359-g007.jpg

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