TY - JOUR
T1 - Identification of RECQ1-regulated transcriptome uncovers a role of RECQ1 in regulation of cancer cell migration and invasion
AU - Li, Xiao Ling
AU - Lu, Xing
AU - Parvathaneni, Swetha
AU - Bilke, Sven
AU - Zhang, Hongen
AU - Thangavel, Saravanabhavan
AU - Vindigni, Alessandro
AU - Hara, Toshifumi
AU - Zhu, Yuelin
AU - Meltzer, Paul S.
AU - Lal, Ashish
AU - Sharma, Sudha
N1 - Funding Information:
This work was funded by the NIGMS/NIH grant 5SC1GM093999-04 to Sudha Sharma and the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and Center for Cancer Research to Ashish Lal. The work in Alessandro Vindigni’s lab was supported by NIH grant R01GM108648. We acknowledge infrastructure support from the NIMHD/NIH under award number G12MD007597.
PY - 2014/8/1
Y1 - 2014/8/1
N2 - 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.
AB - 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.
KW - Cancer
KW - Cell invasion
KW - Cell migration
KW - G4 DNA
KW - Gene expression
KW - Helicase
KW - RecQ
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=84905902659&partnerID=8YFLogxK
U2 - 10.4161/cc.29419
DO - 10.4161/cc.29419
M3 - Article
C2 - 25483193
AN - SCOPUS:84905902659
SN - 1538-4101
VL - 13
SP - 2431
EP - 2445
JO - Cell Cycle
JF - Cell Cycle
IS - 15
ER -