title: URI expression in cervical cancer cells is associated with higher invasion capacity and resistance to cisplatin.
abstract: Cervical cancer is a common and devastating female cancer worldwide. The etiology of cervical cancer has been largely attributed to human papillomavirus (HPV) infection and activation of the P13K/AKT/mTOR (mammalian target of rapamycin) pathway. However, the limited HPV-directed therapy, as well as therapeutic approach targeting P13K/AKT/mTOR pathway, has not yet been established or effective. A deeper understanding of cervical carcinogenesis and finding of novel candidate molecules for cervical cancer therapeutics is largely warranted. The unconventional prefoldin RPB5 interactor (URI or URI1), a known transcription factor involving the TOR signaling pathway, has recently been implicated a role in multiple tumorigenesis. We recently reported significant upregulation of URI in precancerous cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer, suggesting its role in cervical carcinogenesis. However, the effect and underlying mechanism of URI in cervical cancer development have never been elucidated. Here, we aimed to investigate the in vitro effect of URI on cervical cancer using two cervical cancer cell lines CaSki and C33A, which are HPV-positive and HPV-negative respectively. We have shown that forced over-expression of URI in C33A and CaSki cells markedly promoted cell growth, while down-regulation of URI mediated by siRNA inhibited cell proliferation. We have found that URI over-expression enhanced resistance of cervical cancer cells to cisplatin. In contrast, knockdown of URI promoted apoptosis by influencing cell response to cisplatin, supporting URI as an oncogenic protein for cervical cancer cells. We have also shown that URI promoted the migration and invasive capacity of cervical cancer cells by up-regulation of Vimentin, a mesenchymal cell migration marker relating to the epithelial-mesenchymal transition (EMT) program. Our data support an important function of URI in the biological behavior of cervical cancer cells and provide novel mechanistic insights into the role of URI in cervical cancer progression and possibly, metastasis.
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Longwei
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China ; Department of Anatomy and Cell Biology, Rush University Medical Center Chicago, IL, 60612, USA.
authors.forename: Yaojuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Yiyang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China.
authors.forename: Jialu
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Hematology and Hematological Laboratory Science, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, China ; Department of Anatomy and Cell Biology, Rush University Medical Center Chicago, IL, 60612, USA.
authors.forename: Qiping
authors.initials: Q
authors.lastname: Zheng
keywords: C33A and CaSki cell lines; URI; cervical cancer invasive capacity; cisplatin; epithelial-mesenchymal transition; vimentin