Quaking, an RNA-Binding Protein, Is a Critical Regulator of Vascular Smooth Muscle Cell Phenotype

Veer, Eric P. van der; Bruin, Ruben G. de; Kraaijeveld, Adriaan O.; Vries, Margreet R. de; Bot, Ilze; Pera, Tonio; Segers, Filip M.; Trompet, Stella; Gils, Janine M. van; Roeten, Marko K.; Beckers, Cora M.L.; Santbrink, Peter J. van; Janssen, Anique; Solingen, Coen van; Swildens, Jim; Boer, Hetty C. de; Peters, Erna; Bijkerk, Roel; Rousch, Mat; Doop, Merijn; Kuiper, Johan; Schalij, Martin J.; Wal, Allard C. van der; Richard, Stéphane; Berkel, Theo J.C. Van; Pickering, J. Geoffrey; Hiemstra, Pieter S.; Goumans, Marie–José; Rabelink, Ton J.; Vries, Antoine A.F. de; Quax, Paul H.A.; Jukema, J. Wouter; Biessen, Erik A. L.; Zonneveld, Anton Jan van

doi:10.1161/circresaha.113.301302

Cited by 93 publications

(124 citation statements)

References 45 publications

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“…As an RNA-binding protein, QKI post-transcriptionally regulates the mRNA stability, translation efficiency or RNA transportation of target genes via specifically binding to the cis-elements within the 3'-untranslated region (3'UTR) (6)(7)(8)(9)(10). Among these targets, MAG and MBP, which are essential for postnatal myelination are well characterized.…”

Section: Introductionmentioning

confidence: 99%

“…In adult mammals, qki mRNAs can be detected in tissues, such as the heart, skeletal, lung, testes and immune cells in addition to the central nervous system (CNS) (9,(12)(13)(14)(15). In a search for putative RNA targets recognized by QKI, a bipartite consensus sequence ACUAAY-N(1-20)-UAAY was defined as a QKI response element (QRE), and 1,430 putative mRNA targets were identified by bioinformatic analysis (16).…”

Section: Introductionmentioning

confidence: 99%

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Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Jin

Yang

et al. 2013

Oncology Reports

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The RNA-binding protein Quaking (QKI) is known to be essential for embryonic development and postnatal myelination. Forkhead box O1 (FOXO1) is a critical tumor suppressor for cell proliferation control. Dysregulation of FOXO1 expression has been observed in a variety of cancers. In the present study, we demonstrated that QKI decreased FOXO1 mRNA expression at the post-transcriptional level. QKI was able to bind the 3'UTR of FOXO1 mRNA directly and decreased its mRNA stability. To determine whether QKI-mediated post-transcriptional repression of FOXO1 indeed plays a role in cancer cells, we first detected both QKI and FOXO1 expression in four breast cancer cell lines. FOXO1 expression was extremely low in these cell lines, whereas QKI expression was relative high. Knockdown of QKI significantly restored FOXO1 expression. ATRA, an inducer of apoptosis or differentiation, dramatically enhanced FOXO1 expression while it repressed QKI expression. Importantly, the ATRA-induced increase in FOXO1 expression was dependent on QKI-mediated post-transcriptional regulation. Consistently, 5-FU, a widely used chemotherapeutic agent, increased FOXO1 expression via inhibition of QKI. In summary, our study provides initial evidence demonstrating that QKI-mediated repression of FOXO1 may be one of the factors contributing to the oncogenesis and progression of breast carcinoma, which suggests that targeting QKI may serve as a novel strategy to sensitize breast cancers to chemotherapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Jin

Yang

et al. 2013

Oncology Reports

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“…It is well known that QKI plays an important role in the postnatal central nervous system during myelination. Recent studies suggest that it also plays an essential role in blood vessel development [90]. In addition, van der Veer et al [91] observed that QKI is highly expressed in neointimal VSMCs of human coronary restenoticlesions and neointima hyperplasia of mice.…”

Section: Othersmentioning

confidence: 99%

Post-transcriptional gene regulation by RNA-binding proteins in vascular endothelial dysfunction

Xin

Deng

2014

Sci. China Life Sci.

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Endothelial cell dysfunction is a term which implies the dysregulation of normal endothelial cell functions, including impairment of the barrier functions, control of vascular tone, disturbance of proliferative and migratory capacity of endothelial cells, as well as control of leukocyte trafficking. Endothelial dysfunction is an early step in vascular inflammatory diseases such as atherosclerosis, diabetic vascular complications, sepsis-induced or severe virus infection-induced organ injuries. The expressions of inflammatory cytokines and vascular adhesion molecules induced by various stimuli, such as modified lipids, smoking, advanced glycation end products and bacteria toxin, significantly contribute to the development of endothelial dysfunction. The transcriptional regulation of inflammatory cytokines and vascular adhesion molecules has been well-studied. However, the regulation of those gene expressions at post-transcriptional level is emerging. RNA-binding proteins have emerged as critical regulators of gene expression acting predominantly at the post-transcriptional level in microRNA-dependent or independent manners. This review summarizes the latest insights into the roles of RNA-binding proteins in controlling vascular endothelial cell functions and their contribution to the pathogenesis of vascular inflammatory diseases.

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“…Quaking and VSMC Phenotype (p 1065) 59 Blocking an RNA-binding factor called Quaking prevents vascular smooth muscle cells from over-proliferating, report van der Veer et al…”

Section: Fvbmentioning

confidence: 99%

Circulation Research “In This Issue” Anthology

Williams¹

2014

Circulation Research

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Quaking, an RNA-Binding Protein, Is a Critical Regulator of Vascular Smooth Muscle Cell Phenotype

Cited by 93 publications

References 45 publications

Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Post-transcriptional repression of FOXO1 by QKI results in low levels of FOXO1 expression in breast cancer cells

Post-transcriptional gene regulation by RNA-binding proteins in vascular endothelial dysfunction

Circulation Research “In This Issue” Anthology

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