title: Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57.
abstract: Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: E
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: X
authors.initials: X
authors.lastname: He
authors.affiliation: Central Laboratory, The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, China.
authors.forename: D
authors.initials: D
authors.lastname: Yin
authors.affiliation: Department of Oncology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, Jiangsu, China.
authors.forename: L
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: M
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: R
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: L
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Thoracic Surgery, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing, Jiangsu, China.
authors.forename: R
authors.initials: R
authors.lastname: Yin
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: W
authors.initials: W
authors.lastname: De
mesh_terms: D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011379:Prognosis; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D015996:Survival Rate; D014183:Transplantation, Heterologous
chemical_list: C493964:CDKN1C protein, human; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D062085:RNA, Long Noncoding; C000598536:TUG1 long noncoding RNA, human