title: Downregulation of ubiquitin-specific protease 14 (USP14) inhibits breast cancer cell proliferation and metastasis, but promotes apoptosis.
abstract: Breast cancer is the second leading cause of cancer-related death in women. Previously, evidence suggested that ubiquitin-specific protease 14 (USP14) was associated with various signal transduction pathways and tumourigenesis. In this study, we demonstrate that USP14 is a novel therapeutic target in breast cancer. A Western blot analysis of USP14 was performed using seven breast cancer tissues and paired adjacent normal tissues and showed that the expression of USP14 was increased in the breast cancer tissues. Immunohistochemistry was conducted on formalin-fixed paraffin-embedded sections of breast cancer samples from 100 cases. Using Pearson's χ(2) test, it was demonstrated that USP14 expression was associated with the histological grade, lymph node status and Ki-67 expression in the tumour. The Kaplan-Meier analysis revealed that increased USP14 expression in patients with breast cancer was associated with a poorer prognosis. In in vitro experiments, the highly migratory MDA-MB-231 cells that were treated with USP14-shRNA (shUSP14) exhibited decreased motility using Transwell migration assays. Next, we employed a starvation and re-feeding assay, and the CCK-8 assay demonstrated that USP14 regulated breast cancer cell proliferation. Furthermore, we used flow cytometry to analyse cellular apoptosis following USP14 knockdown. Taken together, our results suggested that USP14 was involved in the progression of breast cancer.
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China.|Department of Province Key Laboratory for Information and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Lianxin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: He
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Fulin
authors.initials: F
authors.lastname: Qiang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China.
authors.forename: Changjiang
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China.
authors.forename: Zengya
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China. zhangchunhui1963@sina.com.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Province Key Laboratory for Information and Molecular Drug Target, Nantong University, Nantong, Jiangsu Province, 226001, People's Republic of China. wyy0418@ntu.edu.cn.|Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu Province, People's Republic of China. wyy0418@ntu.edu.cn.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015194:Diffusion Chambers, Culture; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D060787:Neoplasm Grading; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D059016:Tumor Microenvironment; D043222:Ubiquitin Thiolesterase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; C509299:USP14 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Apoptosis; Breast cancer; Migration; Proliferation; USP14