title: Staphylococcal nuclease domain containing-1 (SND1) promotes migration and invasion via angiotensin II type 1 receptor (AT1R) and TGFβ signaling.
abstract: Staphylococcal nuclease domain containing-1 (SND1) is overexpressed in human hepatocellular carcinoma (HCC) patients and promotes tumorigenesis by human HCC cells. We now document that SND1 increases angiotensin II type 1 receptor (AT1R) levels by increasing AT1R mRNA stability. This results in activation of ERK, Smad2 and subsequently the TGFβ signaling pathway, promoting epithelial-mesenchymal transition (EMT) and migration and invasion by human HCC cells. A positive correlation was observed between SND1 and AT1R expression levels in human HCC patients. Small molecule inhibitors of SND1, alone or in combination with AT1R blockers, might be an effective therapeutic strategy for late-stage aggressive HCC.
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Prasanna K
authors.initials: PK
authors.lastname: Santhekadur
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Maaged
authors.initials: M
authors.lastname: Akiel
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Luni
authors.initials: L
authors.lastname: Emdad
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Rachel
authors.initials: R
authors.lastname: Gredler
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Srivastava
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Devaraja
authors.initials: D
authors.lastname: Rajasekaran
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Chadia L
authors.initials: CL
authors.lastname: Robertson
authors.affiliation: Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Nitai D
authors.initials: ND
authors.lastname: Mukhopadhyay
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States ; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, United States ; VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Paul B
authors.initials: PB
authors.lastname: Fisher
authors.affiliation: Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA 23298, United States ; Massey Cancer Center, Virginia Commonwealth University, Richmond, VA 23298, United States ; VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, VA 23298, United States.
authors.forename: Devanand
authors.initials: D
authors.lastname: Sarkar
keywords: ACE, angiotensin-I converting enzyme; ACE-I, ACE inhibitors; AT1R; AT1R, angiotensin II type 1 receptor; EMT, epithelial–mesenchymal transition; FDR, false discovery rate; HCC, human hepatocellular carcinoma; Invasion; LP, losartan potassium; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NASH, non-alcoholic steatohepatitis; PAI-1; PAI-1, plasminogen activator inhibitor-1; RISC, RNA-induced silencing complex; SND1; SND1, Staphylococcal nuclease domain containing-1; TGFβ