title: Specificity protein (Sp) transcription factors and metformin regulate expression of the long non-coding RNA HULC.
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.
authors: Institute of Biosciences and Technology, Texas A&M Health Sciences Center, Houston, TX, USA.
authors: Shruti U
authors: SU
authors: Gandhy
authors: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors: Parisa
authors: P
authors: Imanirad
authors: Institute of Biosciences and Technology, Texas A&M Health Sciences Center, Houston, TX, USA.
authors: Un-Ho
authors: UH
authors: Jin
authors: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors: Vijayalekshmi
authors: V
authors: Nair
authors: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors: Eric
authors: E
authors: Hedrick
authors: Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors: Yating
authors: Y
authors: Cheng
authors: Integrated Systems Toxicology Division, US-EPA, MD B143-06, Research Triangle Park, NC, USA.
authors: J Christopher
authors: JC
authors: Corton
authors: Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
authors: KyoungHyun
authors: K
authors: Kim
authors: 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.
authors: Stephen
authors: S
authors: Safe
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008687:Metformin / Q000494:pharmacology*; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051703:Sp Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; C574685:HULC long non-coding RNA, human; D062085:RNA, Long Noncoding; D051703:Sp Transcription Factors; D008687:Metformin
keywords: HCC; HULC; IncRNAs; Sp proteins