title: E2F1-induced upregulation of long noncoding RNA LINC00668 predicts a poor prognosis of gastric cancer and promotes cell proliferation through epigenetically silencing of CKIs.
abstract: Recently, long noncoding RNAs (lncRNAs) have been shown to have important regulatory roles in human cancer biology. By utilizing publicly available lncRNAs expression profiling data and integrating analyses, we screened out LINC00668, whose expression is significantly increased and correlated with outcomes in gastric cancer (GC). Further experiments revealed that LINC00668 knockdown significantly repressed proliferation, both in vitro and in vivo. Mechanistic investigations showed that LINC00668 was a direct transcriptional target of E2F transcription factor 1 (E2F1). We further demonstrated that LINC00668 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors (CKIs), including p15, p16, p21, p27 and p57, thus contributing to the regulation of the gastric cancer cell cycle. Our results suggest that E2F1-activated LINC00668, as a cell cycle regulator, enriches the mechanistic link between lncRNA and the E2F1-mediated cell cycle regulation pathway and may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Erbao
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Central Laboratory, the Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu, PR China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yin
authors.affiliation: Department of Oncology, Xuzhou Central Hospital, Affiliated Xuzhou Hospital, College of Medicine, Southeast University, Xuzhou, Jiangsu, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Si
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Xia
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Tongpeng
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Dongying
authors.initials: D
authors.lastname: Gu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: De
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Renhua
authors.initials: R
authors.lastname: Guo
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, PR China.|Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu, PR China.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011379:Prognosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D062085:RNA, Long Noncoding; C000611370:long non-coding RNA Linc00675, human
keywords: E2F1; LINC00668; cell cycle; gastric cancer; proliferation