Sp1 cooperates with Sp3 to upregulate MALAT1 expression in human hepatocellular carcinoma.
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, r=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.
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Ziling
Z
Huang
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Lanshan
L
Huang
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Siqiao
S
Shen
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Jia
J
Li
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Huiping
H
Lu
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Weijia
W
Mo
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Yiwu
Y
Dang
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Dianzhong
D
Luo
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Gang
G
Chen
Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Zhenbo
Z
Feng
D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000502:physiology*; D051705:Sp3 Transcription Factor / Q000502:physiology*; D015533:Transcriptional Activation; D015854:Up-Regulation
C557041:MALAT1 long non-coding RNA, human; D062085:RNA, Long Noncoding; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D051705:Sp3 Transcription Factor