title: K-homology splicing regulatory protein (KSRP) promotes post-transcriptional destabilization of Spry4 transcripts in non-small cell lung cancer.
abstract: AU-rich element-binding proteins (ARE-BPs) offer post-transcriptional regulation of gene expression via physical interaction and recruitment of RNA decay machinery to the AU-rich elements within the 3'-UTR of the target transcripts. However, the role of ARE-BPs in lung cancer remains poorly understood. In this study, we have identified that K-homology splicing regulatory protein (KSRP), an ARE-BP, is robustly up-regulated in human lung cancer. Importantly, Kaplan-Meier survival analysis indicated that elevated KSRP expression was correlated with poor overall survival of lung cancer patients. Furthermore, cigarette smoke, a leading risk factor for lung cancer, was also identified to be an important contributor to increased KSRP expression. Remarkably, silencing of KSRP decreased cell proliferation, reversed anchorage-independent growth, and reduced migration/invasion, suggesting an oncogenic role for KSRP in lung cancer. Finally, we provide mechanistic evidence that KSRP promotes the down-regulation of Spry4 by a previously unidentified mechanism,i.e.post-transcriptional mRNA regulation.
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Rama Kamesh
authors.initials: RK
authors.lastname: Bikkavilli
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Sereke Adam
authors.initials: SA
authors.lastname: Zerayesus
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Michelle
authors.initials: M
authors.lastname: Van Scoyk
authors.affiliation: Department of Pathology and Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: Lora
authors.initials: L
authors.lastname: Wilson
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Pei-Ying
authors.initials: PY
authors.lastname: Wu
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Abhinaya
authors.initials: A
authors.lastname: Baskaran
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Ke
authors.initials: K
authors.lastname: Tang
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Syed
authors.initials: S
authors.lastname: Raheem
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Blain A
authors.initials: BA
authors.lastname: Samuelson
authors.affiliation: Division of Developmental Biology and Basic Research, Department of Pediatrics,University of Illinois, Chicago, Illinois 60612.
authors.forename: Narsa M
authors.initials: NM
authors.lastname: Reddy
authors.affiliation: Division of Developmental Biology and Basic Research, Department of Pediatrics,University of Illinois, Chicago, Illinois 60612.
authors.forename: Sekhar P
authors.initials: SP
authors.lastname: Reddy
authors.affiliation: Department of Pathology and Division of Pulmonary Sciences and Critical Care Medicine, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: Carlyne D
authors.initials: CD
authors.lastname: Cool
authors.affiliation: Departments of Physiology, Thoracic Medicine, and Surgery, Lewis Katz School of Medicine and.|Center for Inflammation, Translational, and Clinical Lung Research, Temple University, Philadelphia, Pennsylvania 19140.|Department of Medicine, National Jewish Health, Denver, Colorado 80206, and.
authors.forename: Beata
authors.initials: B
authors.lastname: Kosmider
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and.
authors.forename: Sreedevi
authors.initials: S
authors.lastname: Avasarala
authors.affiliation: From the Division of Pulmonary, Critical Care, Sleep and Allergy, Department of Medicine and rwinn@uic.edu.|Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Winn
mesh_terms: D020413:3' Untranslated Regions; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; C105789:KHSRP protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; C499038:SPRY4 protein, human; D015534:Trans-Activators
keywords: KSRP; NSCLC; RNA-binding protein; Spry4; cell invasion; cell migration; mRNA decay; post-transcriptional regulation