Sp1 cooperates with Sp3 to upregulate MALAT1 expression in human hepatocellular carcinoma

被引：68

作者：

Huang, Ziling ^{[1
]}

Huang, Lanshan ^{[1
]}

Shen, Siqiao ^{[1
]}

Li, Jia ^{[1
]}

Lu, Huiping ^{[1
]}

Mo, Weijia ^{[1
]}

Dang, Yiwu ^{[1
]}

Luo, Dianzhong ^{[1
]}

Chen, Gang ^{[1
]}

Feng, Zhenbo ^{[1
]}

机构：

[1] Guangxi Med Univ, Affiliated Hosp 1, Dept Pathol, Nanning 530021, Guangxi, Peoples R China

来源：

ONCOLOGY REPORTS | 2015年 / 34卷 / 05期

关键词：

hepatocellular carcinoma; transcriptional regulation; Sp1; Sp3; MALAT1; mithramycin A; LONG NONCODING RNA; LUNG-CANCER CELLS; SPECIFICITY PROTEIN-1; PANCREATIC-CANCER; LIVER-CANCER; METASTASIS; MITHRAMYCIN; LNCRNA; TRANSCRIPTION; ACTIVATION;

D O I：

10.3892/or.2015.4259

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), also known as nuclear-enriched transcript 2 (NEAT2), is highly conserved among mammals and highly expressed in the nucleus. It was first identified in lung cancer as a prognostic marker for metastasis but is also associated with several other solid tumors. In hepatocellular carcinoma (HCC), MALAT1 is a novel biomarker for predicting tumor recurrence after liver transplantation. The mechanism of overexpression in tumor progression remains unclear. In the present study, we investigated the role of specificity protein 1/3 (Sp1/3) in regulation of MALAT1 transcription in HCC cells. The results showed a high expression of Sp1, Sp3 and MALAT1 in HCC vs. paired non-tumor liver tissues, which was associated with the AFP level (Sp1, T=7.44, P=0.0064; MALAT1, r=12.37, P=0.0004). Co-silencing of Sp1 and Sp3 synergistically repressed MALAT1 expression. Sp1 binding inhibitor, mithramycin A (MIT), also inhibited MALAT1 expression in HCC cells. In conclusion, the upstream of MALAT1 contains five Sp1/3 binding sites, which may be responsible for MALAT1 transcription. Inhibitors, such as MIT, provide a potential therapeutic strategy for HCC patients with MALAT1 overexpression.

引用

页码：2403 / 2412

页数：10