title: Identification of RECQ1-regulated transcriptome uncovers a role of RECQ1 in regulation of cancer cell migration and invasion.
abstract: The RECQ protein family of helicases has critical roles in protecting and stabilizing the genome. Three of the 5 known members of the human RecQ family are genetically linked with cancer susceptibility syndromes, but the association of the most abundant human RecQ homolog, RECQ1, with cellular transformation is yet unclear. RECQ1 is overexpressed in a variety of human cancers, indicating oncogenic functions. Here, we assessed genome-wide changes in gene expression upon knockdown of RECQ1 in HeLa and MDA-MB-231 cells. Pathway analysis suggested that RECQ1 enhances the expression of multiple genes that play key roles in cell migration, invasion, and metastasis, including EZR, ITGA2, ITGA3, ITGB4, SMAD3, and TGFBR2. Consistent with these results, silencing RECQ1 significantly reduced cell migration and invasion. In comparison to genome-wide annotated promoter regions, the promoters of genes downregulated upon RECQ1 silencing were significantly enriched for a potential G4 DNA forming sequence motif. Chromatin immunoprecipitation assays demonstrated binding of RECQ1 to the G4 motifs in the promoters of select genes downregulated upon RECQ1 silencing. In breast cancer patients, the expression of a subset of RECQ1-activated genes positively correlated with RECQ1 expression. Moreover, high RECQ1 expression was associated with poor prognosis in breast cancer. Collectively, our findings identify a novel function of RECQ1 in gene regulation and indicate that RECQ1 contributes to tumor development and progression, in part, by regulating the expression of key genes that promote cancer cell migration, invasion and metastasis.
authors.affiliation: a Regulatory RNAs and Cancer Section; Genetics Branch; National Cancer Institute; National Institutes of Health; Bethesda, MD USA.
authors.forename: Xiao Ling
authors.initials: XL
authors.lastname: Li
authors.forename: Xing
authors.initials: X
authors.lastname: Lu
authors.forename: Swetha
authors.initials: S
authors.lastname: Parvathaneni
authors.forename: Sven
authors.initials: S
authors.lastname: Bilke
authors.forename: Hongen
authors.initials: H
authors.lastname: Zhang
authors.forename: Saravanabhavan
authors.initials: S
authors.lastname: Thangavel
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vindigni
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hara
authors.forename: Yuelin
authors.initials: Y
authors.lastname: Zhu
authors.forename: Paul S
authors.initials: PS
authors.lastname: Meltzer
authors.forename: Ashish
authors.initials: A
authors.lastname: Lal
authors.forename: Sudha
authors.initials: S
authors.lastname: Sharma
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome
chemical_list: C506725:RECQL protein, human; D053484:RecQ Helicases
keywords: G4 DNA; RecQ; cancer; cell invasion; cell migration; gene expression; helicase; transcription