title: QKI impairs self-renewal and tumorigenicity of oral cancer cells via repression of SOX2.
abstract: Cancer stem cells (CSCs) may contribute to tumor initiation, distant metastasis and chemo-resistance. One of RNA-binding proteins, Quaking (QKI), was reported to be a tumor suppressor. Here we showed that reduced QKI levels were observed in many human oral cancer samples. Moreover further reduction of QKI expression in CSCs was detected compared with non-CSCs in oral cancer cell lines. Overexpressing QKI in oral cancer cells significantly reduced CSC sphere formation and stem cell-associated genes. In tumor implanting nude mice model, QKI significantly impeded tumor initiation rates, tumor sizes and lung metastasis rates. As a contrast, knocking down QKI enhanced the above effects. Among the putative CSC target genes, SOX2 expression was negatively affected by QKI, mechanism study revealed that QKI may directly regulate SOX2 expression via specific binding with its 3'UTR in a cis element-dependent way. Loss of SOX2 even completely reversed the sphere forming ability in QKI knockdown cell line. Taken together, these data demonstrated that SOX2 is an important CSC regulator in oral cancer. QKI is a novel CSC inhibitor and impaired multiple oral CSC properties via partial repression of SOX2. Therefore, reduced expression of QKI may provide a novel diagnostic marker for oral cancer.
authors.affiliation: Department of Oral and Maxillofacial Surgery; School of Stomatology; the Fourth Military Medical University; Xi'an, PR China; Department of Stomatology; 101 Hospital of PLA; Wuxi, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Pharmacogenomics; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Feixue
authors.initials: F
authors.lastname: Feng
authors.affiliation: Department of Oral and Maxillofacial Surgery; School of Stomatology; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Jinke
authors.initials: J
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Pharmacogenomics; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Lu
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Pharmacogenomics; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Pharmacogenomics; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Lu
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Wei
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Biochemistry and Molecular Biology; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Guodong
authors.initials: G
authors.lastname: Yang
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Pharmacogenomics; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Pharmacogenomics; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Zifan
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Oral and Maxillofacial Surgery; School of Stomatology; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Yanpu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Cancer Biology; Department of Pharmacogenomics; the Fourth Military Medical University; Xi'an, PR China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Lei
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C490832:QKI protein, human; D016601:RNA-Binding Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: QKI; SOX2; cancer stem cell; oral cancer; self-renewal