title: A long noncoding RNA Sox2ot regulates lung cancer cell proliferation and is a prognostic indicator of poor survival.
abstract: Sox2 overlapping transcript (Sox2ot) is a long noncoding RNA (lncRNA), localized on human chromosome 3q26.33, which is frequently amplified in lung squamous cell carcinomas (SCCs). However, its roles in lung cancer remain under investigation. In this study, we found that Sox2ot was up-regulated over two folds in 53.01% of human primary lung cancers (44/83). The expression level of Sox2ot is significantly higher in SCCs than that in adenocarcinomas (ADCs) of the lung. Further study found high Sox2ot expression predicted poor survival in lung cancer patients (P=0.0053), implying Sox2ot is a novel prognostic factor. In two human lung cancer cell lines, HCC827 and SK-MES-1, knocking down Sox2ot inhibited cell proliferation by inducing G2/M arrest, with a concomitant decrease of cells in S phase. Reduced protein levels of Cyclin B1 and Cdc2 were also observed. Importantly, knocking down Sox2ot decreased EZH2 expression and reintroduction of EZH2 allowed Sox2ot knockdown cells progressed through G2/M phase, which correlates with the restoration of Cyclin B1 and Cdc2 expressions. Altogether, our data suggested that Sox2ot plays an important role in regulating lung cancer cell proliferation, and may represent a novel prognostic indicator for the disease.
authors.affiliation: First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, Jiangsu, China; Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing 210029, Jiangsu, China.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Hou
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhou
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, Jiangsu, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Shen
authors.affiliation: First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, Jiangsu, China; Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing 210029, Jiangsu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhan
authors.affiliation: First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, Jiangsu, China; Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing 210029, Jiangsu, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Xu
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, Jiangsu, China.
authors.forename: Cunjie
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Bi
authors.affiliation: First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, Jiangsu, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Zou
authors.affiliation: Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Huang
authors.affiliation: First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, Jiangsu, China; Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing 210029, Jiangsu, China. Electronic address: likeyunj@163.com.
authors.forename: Like
authors.initials: L
authors.lastname: Yu
authors.affiliation: MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, Jiangsu, China. Electronic address: yanjun@nju.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
mesh_terms: D000328:Adult; D000368:Aged; D016203:CDC2 Protein Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D056744:Cyclin B1 / Q000096:biosynthesis; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D063151:Polycomb Repressive Complex 2 / Q000096:biosynthesis; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D062085:RNA, Long Noncoding; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: EZH2; Long noncoding RNA; Non-small cell lung cancer; Proliferation; Sox2ot